Generic placeholder image

Coronaviruses

Editor-in-Chief

ISSN (Print): 2666-7967
ISSN (Online): 2666-7975

Review Article

A Recent Update on Therapeutics to Treat Emerging n-COVID 19: A Review

Author(s): Sumel Ashique, Navjot K. Sandhu*, Sk. Niyamul Haque and Kartick Koley

Volume 2, Issue 7, 2021

Published on: 04 December, 2020

Article ID: e250621188724 Pages: 16

DOI: 10.2174/2666796701999201204123259

Abstract

A coronavirus is a group of nonsegmented, single-stranded, enveloped viruses having positive RNA genomes. This virus was first described in 1931, and the first coronavirus was isolated (HCoV-229E) from humans in 1965. People be-come infected with four human coronavirus strains: 229E, NL63, OC43, and HKU1, which cause respiratory associated problems such as SARS and MERS. Lately, a new version of a strain called SARD-CoV-2 has been found. WHO called it novel coronavirus-infected pneumonia (NCIP) and later officially renamed as COVID-19 on 11th Feb 2020. The outbreak began in Wuhan, Hubei, China, in Dec 2019 and from now the outbreak becomes pandemic. Here, we have reviewed various categories of therapeutics, vaccines, and clinically investigated drugs to treat and prevent n-COVID-19. Till now, no specific FDA approved drugs or vaccines are available against n-COVID-19. Several options can be visualized to control or prevent emerging infections, including antivirals, immunomodulators, interferons, vaccines, monoclonal antibodies, and bio- molecules. Given the urgency of the outbreak, we have discussed some potential existing therapeutics for treating n-COVID-19.

Keywords: n-COVID-19, therapeutics, vaccines, coronaviruses, monoclonal antibodies, RNA vaccine.

Graphical Abstract

[1]
Klompas M, Baker MA, Rhee C. Airborne transmission of SARS- CoV-2: Theoretical considerations and available evidence. JAMA 2020; 324(5): 441-2.
[http://dx.doi.org/10.1001/jama.2020.12458] [PMID: 32749495]
[2]
Te HS, Randall G, Jensen DM. Mechanism of action of ribavirin in the treatment of chronic hepatitis C. Gastroenterol Hepatol (NY) 2007; 3(3): 218-25.
[PMID: 21960835]
[3]
Barnard DL, Day CW, Bailey K, et al. Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase inhibitors, including ribavirin. Antiviral Res 2006; 71(1): 53-63.
[http://dx.doi.org/10.1016/j.antiviral.2006.03.001] [PMID: 16621037]
[4]
Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289(21): 2801-9.
[http://dx.doi.org/10.1001/jama.289.21.JOC30885] [PMID: 12734147]
[5]
Falzarano D, de Wit E, Rasmussen AL, et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 2013; 19(10): 1313-7.
[http://dx.doi.org/10.1038/nm.3362] [PMID: 24013700]
[6]
Omrani AS, Saad MM, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis 2014; 14(11): 1090-5.
[http://dx.doi.org/10.1016/S1473-3099(14)70920-X] [PMID: 25278221]
[7]
Shalhoub S, Farahat F, Al-Jiffri A, et al. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother 2015; 70(7): 2129-32.
[http://dx.doi.org/10.1093/jac/dkv085] [PMID: 25900158]
[8]
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9: eaal3653.
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[9]
Pyrc K, Bosch BJ, Berkhout B, et al. Inhibition of human coronavirus NL63 infection at early stages of the replication cycle. Antimicrob Agents Chemother 2006; 50(6): 2000-8.
[http://dx.doi.org/10.1128/AAC.01598-05] [PMID: 16723558]
[10]
Barnard DL, Hubbard VD, Burton J, et al. Inhibition of severe acute respiratory syndrome-associated coronavirus (SARSCoV) by calpain inhibitors and β-D-N4-hydroxycytidine. Antivir Chem Chemother 2004; 15(1): 15-22.
[http://dx.doi.org/10.1177/095632020401500102] [PMID: 15074711]
[11]
Taylor R, Kotian P, Warren T, et al. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease. J Infect Public Health 2016; 9(3): 220-6.
[http://dx.doi.org/10.1016/j.jiph.2016.04.002] [PMID: 27095300]
[12]
Saijo M, Morikawa S, Fukushi S, et al. Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus. Antiviral Res 2005; 66(2-3): 159-63.
[http://dx.doi.org/10.1016/j.antiviral.2005.01.003] [PMID: 15911031]
[13]
Peters HL, Jochmans D, de Wilde AH, et al. Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity. Bioorg Med Chem Lett 2015; 25(15): 2923-6.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.039] [PMID: 26048809]
[14]
Shoemaker CJ, Schornberg KL, Delos SE, et al. Multiple cationic amphiphiles induce a Niemann-Pick C phenotype and inhibit Ebola virus entry and infection. PLoS One 2013; 8(2): e56265.
[http://dx.doi.org/10.1371/journal.pone.0056265] [PMID: 23441171]
[15]
Bleibtreu A, Jaureguiberry S, Houhou N, et al. Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016. BMC Infect Dis 2018; 18(1): 331-40.
[http://dx.doi.org/10.1186/s12879-018-3223-5] [PMID: 30012113]
[16]
Tan EL, Ooi EE, Lin CY, et al. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs Emerg Infect Dis 2004; 10(4): 581-6.
[http://dx.doi.org/10.3201/eid1004.030458] [PMID: 15200845]
[17]
Al-Abdely HM, Midgley CM, Alkhamis AM, et al. Middle East respiratory syndrome coronavirus infection dynamics and antibody responses among clinically diverse patients, Saudi Arabia. Emerg Infect Dis 2019; 25(4): 753-66.
[http://dx.doi.org/10.3201/eid2504.181595] [PMID: 30882305]
[18]
Saeed AA, Abedi GR, Alzahrani AG, et al. Surveillance and testing for Middle East respiratory syndrome coronavirus, Saudi Arabia, April 2015– February 2016. Emerg Infect Dis 2017; 23(4): 682-5.
[http://dx.doi.org/10.3201/eid2304.161793] [PMID: 28322710]
[19]
Oldfield V, Plosker GL. Lopinavir/ritonavir: A review of its use in the management of HIV infection. Drugs 2006; 66(9): 1275-99.
[http://dx.doi.org/10.2165/00003495-200666090-00012] [PMID: 16827606]
[20]
Chu CM, Cheng VC, Hung IF, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax 2004; 59(3): 252-6.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[21]
Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4-26.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[22]
Dayer MR, Taleb-Gassabi S, Dayer MS. Lopinavir; a potent drug against coronavirus infection: insight from molecular docking study. Arch Clin Infect Dis 2017; 12: e13823-30.
[http://dx.doi.org/10.5812/archcid.13823]
[23]
Yamamoto N, Yang R, Yoshinaka Y, et al. HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus. Biochem Biophys Res Commun 2004; 318(3): 719-25.
[http://dx.doi.org/10.1016/j.bbrc.2004.04.083] [PMID: 15144898]
[24]
Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy 2016; 8(8): 959-70.
[http://dx.doi.org/10.2217/imt-2016-0020] [PMID: 27381687]
[25]
Arabi YM, Mandourah Y, Al-Hameed F, et al. Saudi critical care trial group. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med 2018; 197(6): 757-67.
[http://dx.doi.org/10.1164/rccm.201706-1172OC] [PMID: 29161116]
[26]
Auyeung TW, Lee JS, Lai WK, et al. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: A retrospective cohort study. J Infect 2005; 51(2): 98-102.
[http://dx.doi.org/10.1016/j.jinf.2004.09.008] [PMID: 16038758]
[27]
Ho JC, Ooi GC, Mok TY, et al. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. Am J Respir Crit Care Med 2003; 168(12): 1449-56.
[http://dx.doi.org/10.1164/rccm.200306-766OC] [PMID: 12947028]
[28]
Yam LY, Lau AC, Lai FY, Shung E, Chan J, Wong V. Hong Kong Hospital Authority SARS Collaborative Group (HASCOG). Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong. J Infect 2007; 54(1): 28-39.
[http://dx.doi.org/10.1016/j.jinf.2006.01.005] [PMID: 16542729]
[29]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[30]
Lee N, Leo YS, Cao B, et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J 2015; 45(6): 1642-52.
[http://dx.doi.org/10.1183/09031936.00169714] [PMID: 25573405]
[31]
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020; 46(5): 846-8.
[http://dx.doi.org/10.1007/s00134-020-05991-x] [PMID: 32125452]
[32]
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
[http://dx.doi.org/10.1016/S0140-6736(20)30317-2] [PMID: 32043983]
[33]
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061-9.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[35]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[36]
36. U.S. national institutes of health. Methylprednisolone for patients with COVID-19 severe acute respiratory syndrome (MP-C19) Available from https://clinicaltrials.gov/ct2/show/record/NCT04323592
[37]
Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther 2020; 5(1): 57.
[http://dx.doi.org/10.1038/s41392-020-0158-2] [PMID: 32341331]
[38]
Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020; 395(10225): 683-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30361-5] [PMID: 32122468]
[39]
Medium. medrol: A drug like dexamethasone that also works against Covid-19. Available from: https://medium.com/microbial-instincts/medrol-a-drug-like-dexamethasone-that-also-works-against-covid-19-1b72479fff1e
[40]
Medscape. What is the role of corticosteroids (such as dexamethasone) in the treatment of coronavirus disease. 2019. Available from: https://www.medscape.com/answers/2500114-197459/what-is-the-role-of-corticosteroids-such-as-dexamethasone-in-the-treatment-of-coronavirus-disease-2019-covid-19
[41]
Zheng W, Ed. Shanghai clinical treatment expert group for corona virus disease 2019. Comprehensive treatment and management of corona virus disease 2019: expert consensus statement from Shanghai.COVID-19. Singapore: World Scientific Publishing Co Pte Ltd 2020; pp. 226-44.
[42]
Luo J, Rizvi H, Egger JV, Preeshagul IR, Wolchok JD, Hellmann MD. Impact of PD-1 blockade on severity of COVID-19 in patients with lung cancers. Cancer Discov 2020; 10(8): 1121-8.
[http://dx.doi.org/10.1158/2159-8290.CD-20-0596] [PMID: 32398243]
[43]
Laterre PF, François B, Collienne C, et al. Association of interleukin 7 immunotherapy with lymphocyte counts among patients with severe coronavirus disease 2019 (covid-19). JAMA Netw Open 2020; 3(7): e2016485.
[http://dx.doi.org/10.1001/jamanetworkopen.2020.16485] [PMID: 32697322]
[44]
Zhao Z, Zhang F, Xu M, et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J Med Microbiol 2003; 52(Pt 8): 715-20.
[http://dx.doi.org/10.1099/jmm.0.05320-0] [PMID: 12867568]
[45]
Hensley LE, Fritz LE, Jahrling PB, Karp CL, Huggins JW, Geisbert TW. Interferon-β 1a and SARS coronavirus replication. Emerg Infect Dis 2004; 10(2): 317-9.
[http://dx.doi.org/10.3201/eid1002.030482] [PMID: 15030704]
[46]
Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep 2013; 3: 1686-92.
[http://dx.doi.org/10.1038/srep01686] [PMID: 23594967]
[47]
Cao W, Liu X, Bai T, et al. Recovery of severely ill COVID-19 patients by intravenous immunoglobulin (IVIG) treatment: A case series. Virology 2020; 548: 1-5.
[http://dx.doi.org/10.1016/j.virol.2020.05.006] [PMID: 32530808]
[48]
Mohtadi N, Ghaysouri A, Shirazi S, et al. Recovery of severely ill COVID-19 patients by intravenous immunoglobulin (IVIG) treatment: A case series. Virology 2020; 548: 1-5.
[http://dx.doi.org/10.1016/j.virol.2020.05.006] [PMID: 32530808]
[49]
Pipelinereview. octapharma reports positive data from octagam® usage in critically ill covid-19 patients. Available from: https://pipelinereview.com/index.php/2020071575304/Antibodies/Octapharma-Reports-Positive-Data-from-octagam-Usage-in-Critically-Ill-COVID-19-Patients.html
[50]
Kandeil A, Gomaa M, Shehata M, et al. Middle East respiratory syndrome coronavirus infection in non-camelid domestic mammals. Emerg Microbes Infect 2019; 8(1): 103-8.
[http://dx.doi.org/10.1080/22221751.2018.1560235] [PMID: 30866764]
[51]
CDC. Multisystem inflammatory syndrome (MIS-C). Available from https://www.cdc.gov/mis-c/
[52]
Liu Y, Yan LM, Wan L, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis 2020; 20(6): 656-7.
[http://dx.doi.org/10.1016/S1473-3099(20)30232-2] [PMID: 32199493]
[53]
Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics 2020; 145(6): e20200702.
[http://dx.doi.org/10.1542/peds.2020-0702] [PMID: 32179660]
[54]
Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020; 369: m2094.
[http://dx.doi.org/10.1136/bmj.m2094] [PMID: 32493739]
[55]
Fuchs TA, Abed U, Goosmann C, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 2007; 176(2): 231-41.
[http://dx.doi.org/10.1083/jcb.200606027] [PMID: 17210947]
[56]
Hiroki CH, Toller-Kawahisa JE, Fumagalli MJ, et al. Neutrophil extracellular traps effectively control acute chikungunya virus infection. Front Immunol 2020; 10: 3108.
[http://dx.doi.org/10.3389/fimmu.2019.03108] [PMID: 32082301]
[57]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[58]
Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020; 191: 145-7.
[http://dx.doi.org/10.1016/j.thromres.2020.04.013] [PMID: 32291094]
[59]
Baden LR, Rubin EJ. Covid-19—the search for effective therapy. N Engl J Med 2020; 382(19): 1851-2.
[http://dx.doi.org/10.1056/NEJMe2005477] [PMID: 32187463]
[60]
Zuo Y, Yalavarthi S, Shi H, et al. Neutrophil extracellular traps in COVID-19. JCI Insight 2020; 5(11): e138999.
[PMID: 32329756]
[61]
Borissoff JI, Joosen IA, Versteylen MO, et al. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 2013; 33(8): 2032-40.
[http://dx.doi.org/10.1161/ATVBAHA.113.301627] [PMID: 23818485]
[62]
Whittaker E, Bamford A, Kenny J, et al. PIMS-TS study group and EUCLIDS and perform consortia. Clinical Characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324(3): 259-69.
[http://dx.doi.org/10.1001/jama.2020.10369] [PMID: 32511692]
[63]
Grimaud M, Starck J, Levy M, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intensive Care 2020; 10(1): 69-8.
[http://dx.doi.org/10.1186/s13613-020-00690-8] [PMID: 32488505]
[64]
Hennon TR, Penque MD, Abdul-Aziz R, et al. COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) guidelines; a Western New York approach. Prog Pediatr Cardiol 2020; 57: 10123.
[http://dx.doi.org/10.1016/j.ppedcard.2020.101232] [PMID: 32837142]
[65]
Jiang L, Tang K, Levin M, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020; 20: e276-88.
[http://dx.doi.org/10.1016/S1473-3099(20)30651-4] [PMID: 32818434]
[66]
Tolouian R, Vahed SZ, Ghiyasvand S, Tolouian A, Ardalan M. COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment. J Renal Inj Prev 2020; 9(2): e19.
[http://dx.doi.org/10.34172/jrip.2020.19]
[67]
Monteil V, Kwon H, Prado P, et al. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 2020; 181(4): 905-913.e7.
[http://dx.doi.org/10.1016/j.cell.2020.04.004] [PMID: 32333836]
[68]
Lu RM, Hwang YC, Liu IJ, et al. Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 2020; 27(1): 1-30.
[http://dx.doi.org/10.1186/s12929-019-0592-z] [PMID: 31894001]
[69]
Wong SK, Li W, Moore MJ, Choe H, Farzan M. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem 2004; 279(5): 3197-201.
[http://dx.doi.org/10.1074/jbc.C300520200] [PMID: 14670965]
[70]
van den Brink EN, Ter Meulen J, Cox F, et al. Molecular and biological characterization of human monoclonal antibodies binding to the spike and nucleocapsid proteins of severe acute respiratory syndrome coronavirus. J Virol 2005; 79(3): 1635-44.
[http://dx.doi.org/10.1128/JVI.79.3.1635-1644.2005] [PMID: 15650189]
[71]
Cheng Y, Wong R, Soo YO, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis 2005; 24(1): 44-6.
[http://dx.doi.org/10.1007/s10096-004-1271-9] [PMID: 15616839]
[72]
Sui J, Li W, Murakami A, et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci USA 2004; 101(8): 2536-41.
[http://dx.doi.org/10.1073/pnas.0307140101] [PMID: 14983044]
[73]
Ou J, Zhou Z, Dai R, et al. Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein. bioRxiv 2020. 03.15.991844
[74]
Wang C, Li W, Drabek D, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 2020; 11(1): 1-6.
[http://dx.doi.org/10.1038/s41467-020-16256-y] [PMID: 31911652]
[75]
Wu Y, Wang F, Shen C, et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science 2020; 368(6496): 1274-8.
[http://dx.doi.org/10.1126/science.abc2241] [PMID: 32404477]
[76]
Hospimedica international staff writers. New research collaboration to develop combination of monoclonal antibody and natural killer cells as treatment for COVID-19. Available from: https://www.hospimedica.com/covid-19/articles/294784092/new-research-collaboration-to-develop-combination-of-monoclonal-antibody-and-natural-killer-cells-as-treatment-for-covid-19.html
[77]
Ravelo JL. DevExplains: Monoclonal antibody treatment for COVID-19. Available from: https://www.devex.com/news/devexplains-monoclonal-antibody-treatment-for-covid-19-97708
[78]
Miller SG. launches clinical trials for COVID-19 monoclonal antibody treatment. Available from: https://www.nbcnews.com/health/health-news/nih-launches-clinical-trials-covid-19-monoclonal-antibody-treatment-n1235753
[79]
Charters L. Human monoclonal antibody a possible treatment for ARDS in COVID-19. Available from: https://www.ophthalmologytimes.com/view/human-monoclonal-antibody-a-possible-treatment-for-ards-in-covid-19
[80]
ter Meulen J, van den Brink EN, Poon LL, et al. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 2006; 3(7): e237.
[http://dx.doi.org/10.1371/journal.pmed.0030237] [PMID: 16796401]
[81]
Berry JD, Hay K, Rini JM, et al. Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology. MAbs 2010; 2(1): 56-66.
[82]
Ng OW, Keng CT, Leung CS, Peiris JS, Poon LL, Tan YJ. Substitution at aspartic acid 1128 in the SARS coronavirus spike glycoprotein mediates escape from a S2 domain-targeting neutralizing monoclonal antibody. PLoS One 2014; 9(7): e102415.
[http://dx.doi.org/10.1371/journal.pone.0102415] [PMID: 25019613]
[83]
Elshabrawy HA, Coughlin MM, Baker SC, Prabhakar BS. Human monoclonal antibodies against highly conserved HR1 and HR2 domains of the SARS-CoV spike protein are more broadly neutralizing. PLoS One 2012; 7(11): e50366.
[http://dx.doi.org/10.1371/journal.pone.0050366] [PMID: 23185609]
[84]
Walls AC, Xiong X, Park YJ, et al. Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell 2019; 176(5): 1026-1039.e15.
[http://dx.doi.org/10.1016/j.cell.2018.12.028] [PMID: 30712865]
[85]
Greenough TC, Babcock GJ, Roberts A, et al. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J Infect Dis 2005; 191(4): 507-14.
[http://dx.doi.org/10.1086/427242] [PMID: 15655773]
[86]
Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020; 323(16): 1582-9.
[http://dx.doi.org/10.1001/jama.2020.4783] [PMID: 32219428]
[87]
Joyner M, Wright RS, Fairweather D, et al. al. Early safety indicators of COVID-19 convalescent plasma in 5,000 patients. medRxiv 2020.
[88]
Liu ST, Lin HM, Baine I, et al. Convalescent plasma treatment of severe COVID-19: A matched control study. medRxiv 2020.
[89]
Zhang W, Zhao Y, Zhang F, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol 2020; 214: 108393-8.
[http://dx.doi.org/10.1016/j.clim.2020.108393] [PMID: 32222466]
[90]
Genentech Initiates Phase III clinical trial of actemra in hospitalized patients with severe COVID-19 pneumonia. Available from: https://www.gene.com/media/press-releases/14841/2020-03-18/genentech-initiates-phase-iii-clinical-t
[91]
Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet 2020; 395(10223): e30-1.
[http://dx.doi.org/10.1016/S0140-6736(20)30304-4] [PMID: 32032529]
[92]
Dyall J, Coleman CM, Hart BJ, et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 2014; 58(8): 4885-93.
[http://dx.doi.org/10.1128/AAC.03036-14] [PMID: 24841273]
[93]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020; 19(3): 149-50.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
[94]
Pharmaceutical Technology. Favilavir approved as experimental coronavirus drug. Available from: https://www.pharmaceutical-technology.com/news/china-favilavir-testing-approval
[95]
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2. Antiviral Res in vitro 2020; 178: 104787.
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[96]
Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol 2007; 81(18): 9812-24.
[http://dx.doi.org/10.1128/JVI.01012-07] [PMID: 17596301]
[97]
Chen H, Zhang Z, Wang L, et al. First Clinical study using HCV protease inhibitor danoprevir to treat naive and experienced COVID-19 patients. MedRxiv 2020.
[98]
Drug Target Review. Nafamostat inhibits SARS-CoV-2 infection, preventing COVID-19 transmission. Available from: https://www.drugtargetreview.com/news/58915/nafamostat-inhibits-sars-cov-2-infection-preventing-covid-19-transmission
[99]
Clinical trials arena. Largest Covid-19 trials studying Umifenovir or traditional Chinese medicine. Available from: https://www.clinicaltrialsarena.com/comment/covid-19-clinical-trials
[100]
Clinical trials. Bevacizumab in severe or critical patients with COVID-19 pneumonia (BEST-CP. Available from: https://clinicaltrials.gov/ct2/show/NCT04275414
[101]
Solaimanzadeh I. Acetazolamide, nifedipine and phosphodiesterase inhibitors: rationale for their utilization as adjunctive countermeasures in the treatment of coronavirus disease 2019 (COVID-19). Cureus 2020; 12(3): e7343-8.
[http://dx.doi.org/10.7759/cureus.7343] [PMID: 32226695]
[102]
Tufan A, Avanoğlu Güler A, Matucci-Cerinic M. COVID-19, immune system response, hyperinflammation and repurposing antirheumatic drugs. Turk J Med Sci 2020; 50(SI-1): 620-32.
[http://dx.doi.org/10.3906/sag-2004-168] [PMID: 32299202]
[103]
Huet T, Beaussier H, Voisin O, et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol 2020; 2(7): e393-400.
[http://dx.doi.org/10.1016/S2665-9913(20)30164-8] [PMID: 32835245]
[104]
Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+ CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv 2020.
[http://dx.doi.org/10.1101/2020.02.12.945576]
[105]
Al Ghamdi M, Alghamdi KM, Ghandoora Y, et al. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis 2016; 16(1): 174.
[http://dx.doi.org/10.1186/s12879-016-1492-4] [PMID: 27097824]
[107]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV). in vitroCell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[108]
Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol 2009; 7(3): 226-36.
[http://dx.doi.org/10.1038/nrmicro2090] [PMID: 19198616]
[109]
Okba NM, Raj VS, Haagmans BL. Middle East respiratory syndrome coronavirus vaccines: current status and novel approaches. Curr Opin Virol 2017; 23: 49-58.
[http://dx.doi.org/10.1016/j.coviro.2017.03.007] [PMID: 28412285]
[110]
News details. Inovio accelerates timeline for COVID-19 DNA vaccine INO-4800. Available from: https://ir.inovio.com/news-releases/news-releases-details/2020/Inovio-Accelerates-Timeline-for-COVID-19-DNA-Vaccine-INO-4800/default.aspx
[111]
Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines - a new era in vaccinology. Nat Rev Drug Discov 2018; 17(4): 261-79.
[http://dx.doi.org/10.1038/nrd.2017.243] [PMID: 29326426]
[112]
Press releases. Moderna ships mRNA vaccine against novel coronavirus (mRNA-1273) for phase 1 study. Available from https://investors.modernatx.com/news-releases/news-release-details/moderna-ships-mrna-vaccine-against-novel-coronavirus-mrna-1273
[113]
Oxford Vaccine group. COVID-19 vaccine development. Available from: ovg.ox.ac.uk/news/covid-19-vaccine-development
[114]
Kalinga. TB vaccine to fight Covid-19, Texas A&M kicks off human trials. Available from: https://kalingatv.com/nation/tb-vaccine-to-fight-covid-19-texas-am-kicks-off-human-trials
[115]
Bharat Biotech. COVAXIN® - India's first indigenous COVID-19 vaccine. Available from: https://www.bharatbiotech.com/covaxin.html
[116]
Thanh Le T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov 2020; 19: 305-6.
[http://dx.doi.org/10.1038/d41573-020-00073-5] [PMID: 32273591]
[117]
European pharmaceutical review. Potential COVID-19 therapeutics currently in development. Available from: https://www.europeanpharmaceuticalreview.com/article/115842/potential-covid-19-therapeutics-currently-in-development
[118]
Liu J, Zheng X, Huang Y, Shan H, Huang J. Successful use of methylprednisolone for treating severe COVID-19. J Allergy Clin Immunol 2020; 146(2): 325-7.
[http://dx.doi.org/10.1016/j.jaci.2020.05.021] [PMID: 32479759]
[119]
HospiMedica International staff writers. New lab-based studies show two existing drugs inhibit SARS-CoV-2 from infecting human cells. Available from: https://www.hospimedica.com/covid-19/articles/294784081/new-lab-based-studies-show-two-existing-drugs-inhibit-sars-cov-2-from-infecting-human-cells.html
[120]
HospiMedica International staff writers. Clinical trial to test cystic fibrosis drug in patients with severe COVID-19 pneumonia and respiratory failure. Available from: https://www.hospimedica.com/covid-19/articles/294784083/clinical-trial-to-test-cystic-fibrosis-drug-in-patients-with-severe-covid-19-pneumonia-and-respiratory-failure.html
[121]
HospiMedica International staff writers. Engineered decoy ACE2 receptors that neutralize coronavirus and block infection could directly treat COVID-19. Available from: https://www.hospimedica.com/covid-19/articles/294784082/engineered-decoy-ace2-receptors-that-neutralize-coronavirus-and-block-infection-could-directly-treat-covid-19.html
[122]
Clinical trials. Results. Available from: https://clinicaltrials.gov/ct2/results

© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version492msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[08:46:49] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[08:46:49] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[08:46:49] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[08:46:49] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (107ms)time
  • Application (385ms)time
  • 1 x Application (78.32%)
    385ms
    1 x Booting (21.68%)
    107ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    34 statements were executed, 4 of which were duplicates, 30 unique. Show only duplicated291ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('314508452','',1,1740473209,1740473209) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1740473209
      1.87msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('314508452','/article/112063',1,1740473209,1740473209)
      200μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 314508452 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 314508452) limit 1
      19.14msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 314508452
      • 1: 314508452
      • 2: 314508452
      • 3: 314508452
      • 4: 314508452
      • 5: 314508452
      • 6: 314508452
      • 7: 314508452
      • 8: 314508452
      • 9: 314508452
      • 10: 314508452
      • 11: 314508452
      • 12: 314508452
      • 13: 314508452
      • 14: 314508452
      • 15: 314508452
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=112063
      1.39msalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 190 limit 1
      570μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 190
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=190) and sj.journal_id!=190 group by `j`.`nid`) as `aggregate_table`
      1.34msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=190) and sj.journal_id!=190 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      900μsalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=190) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      2.32msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=190) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      1.1msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '112063'
      1.72msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 112063
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '112063'
      3.95msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 112063
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '112063' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.43msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 112063
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      260μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      490μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 190 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      38.12msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 190 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      4.62msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 190 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      3.04msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 112063 limit 1
      340μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 112063
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 112063 and content_type = 'article' order by status desc limit 1
      430μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid article_nid,a.title article_title,j.title journal_title from content_by_diseases cd inner join article a on a.article_id=cd.content_id inner join journal j on j.journal_id=a.journal_id where cd.pid = 295 and cd.sub_disease_id = 300 and content_id!=112063 and cd.content_type = 'article' order by rand() limit 20
      198msalphaeurekaselec_live_10_06_2022Article.php#769
      Backtrace
      • 11. app/Models/Article.php:769
      • 12. app/Http/Controllers/ArticleController.php:2098
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 188724 limit 1
      280μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 188724
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      280μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'COVID' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      340μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: COVID
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '112063' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      490μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '10738' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      380μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3027' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      370μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '7' and is_uploaded = 1 and issue_id = 10738 order by cast(first_page as SIGNED) desc limit 1
      520μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 7
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '22' and is_uploaded = 1 and issue_id = 10738 order by cast(first_page as SIGNED) asc limit 1
      450μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 22
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      190μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      230μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 112063 limit 1
      2.36msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 112063
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 190 and `b`.`banner_from_date` <= 1740473209 and `b`.`banner_to_date` >= 1740473209 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.14msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 190
      • 3: 1740473209
      • 4: 1740473209
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 190 and `b`.`banner_from_date` <= 1740473209 and `b`.`banner_to_date` >= 1740473209 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 190
      • 3: 1740473209
      • 4: 1740473209
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='381695ede7422238277015c25658f5ee'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        n1lo8U5S3ssWVSii6Q9qfJpF87JEkYzbTyljJzLa
        uc_cart_id
        381695ede7422238277015c25658f5ee
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/112063" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/112063
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:8 [ "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        []
        
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 08:46:49 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlU0VTJJK3FicDd1ZGJOamJjeE51RUE9PSIsInZhbHVlIjoiNExVZVBPQmpJRzd2My9qZGNnQStJL1dVYjVzcldnUVBjMFcxZXlrNEVjbnhoeEdiK0ZERGRGV05ISHBURWZOWC9LZlJ5YjkvME0zZThscStCODQ2QXQzZnJqcEZ0SFVaSS91T1FqMVhWRExUNTkwU0NvbG8rVnk4STI5ZzFxL3YiLCJtYWMiOiJmOTQ5MWE1Y2JhZGI1Y2YxMWY1NDM0NzJmN2Q3MGEzYTk5ZDQxMzY4NmYyZDY4N2VkMzk5OTE1NWY3NzJmNzk1IiwidGFnIjoiIn0%3D; expires=Thu, 27 Feb 2025 20:46:49 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IlU0VTJJK3FicDd1ZGJOamJjeE51RUE9PSIsInZhbHVlIjoiNExVZVBPQmpJRzd2My9qZGNnQStJL1dVYjVzcldnUVBjMFcxZXlrNEVjbnhoeEdiK0ZERGRGV05ISHBURWZOWC9LZlJ5Y" 1 => "alphaeurekaselectnet_session=eyJpdiI6IktuejVqYndadTlwTDdjSTltWnRQVWc9PSIsInZhbHVlIjoiOUQ1bENxZW9VRjd0eTN0UmJFSVBvSktyUm9tSUZ3SngzeVBxOGo4RlcvandwSFR3L3JicEE1YU9MMVkyVS82UnFJWWo5UVBrRk01TjF1dkh3TnYxN2kwOEw1MGpjMG1vMGN5WnAyc0tXbWtPa1RxWW52Vmo0WFFjL3QyT2hWS0giLCJtYWMiOiI0N2M4YzMyYWYyZDBhOTcxMDljYWU0ODZjZTc2ZmY1NDE3MDllYTdhNjkzMWFjMjQ3ODM5NGQ4ZmM2MGM5ZDY0IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6IktuejVqYndadTlwTDdjSTltWnRQVWc9PSIsInZhbHVlIjoiOUQ1bENxZW9VRjd0eTN0UmJFSVBvSktyUm9tSUZ3SngzeVBxOGo4RlcvandwSFR3L3JicEE1YU9" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IlU0VTJJK3FicDd1ZGJOamJjeE51RUE9PSIsInZhbHVlIjoiNExVZVBPQmpJRzd2My9qZGNnQStJL1dVYjVzcldnUVBjMFcxZXlrNEVjbnhoeEdiK0ZERGRGV05ISHBURWZOWC9LZlJ5YjkvME0zZThscStCODQ2QXQzZnJqcEZ0SFVaSS91T1FqMVhWRExUNTkwU0NvbG8rVnk4STI5ZzFxL3YiLCJtYWMiOiJmOTQ5MWE1Y2JhZGI1Y2YxMWY1NDM0NzJmN2Q3MGEzYTk5ZDQxMzY4NmYyZDY4N2VkMzk5OTE1NWY3NzJmNzk1IiwidGFnIjoiIn0%3D; expires=Thu, 27-Feb-2025 20:46:49 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IlU0VTJJK3FicDd1ZGJOamJjeE51RUE9PSIsInZhbHVlIjoiNExVZVBPQmpJRzd2My9qZGNnQStJL1dVYjVzcldnUVBjMFcxZXlrNEVjbnhoeEdiK0ZERGRGV05ISHBURWZOWC9LZlJ5Y" 1 => "alphaeurekaselectnet_session=eyJpdiI6IktuejVqYndadTlwTDdjSTltWnRQVWc9PSIsInZhbHVlIjoiOUQ1bENxZW9VRjd0eTN0UmJFSVBvSktyUm9tSUZ3SngzeVBxOGo4RlcvandwSFR3L3JicEE1YU9MMVkyVS82UnFJWWo5UVBrRk01TjF1dkh3TnYxN2kwOEw1MGpjMG1vMGN5WnAyc0tXbWtPa1RxWW52Vmo0WFFjL3QyT2hWS0giLCJtYWMiOiI0N2M4YzMyYWYyZDBhOTcxMDljYWU0ODZjZTc2ZmY1NDE3MDllYTdhNjkzMWFjMjQ3ODM5NGQ4ZmM2MGM5ZDY0IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6IktuejVqYndadTlwTDdjSTltWnRQVWc9PSIsInZhbHVlIjoiOUQ1bENxZW9VRjd0eTN0UmJFSVBvSktyUm9tSUZ3SngzeVBxOGo4RlcvandwSFR3L3JicEE1YU9" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "n1lo8U5S3ssWVSii6Q9qfJpF87JEkYzbTyljJzLa" "uc_cart_id" => "381695ede7422238277015c25658f5ee" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/112063" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 08:46:49GET/article/112063414341