SARS-CoV-2 Therapy: Old Drugs as New Interventions

Puneet    K.    Samaiya; Mahendra       Kumar
doi:10.2174/2666796701999200721003212
Abstract

An outburst of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a grave threat to global health and the economy. As of May 13, 2020, a total of 42,81,838 cases have been confirmed, with over 2,92,376 deaths worldwide. In India, 75,048 cases have been reported to date with 2,440 deaths. Management of this new coronavirus (COVID19) has mainly focused on infection prevention, case detection, monitoring, and supportive care. As there is no vaccine or specific antiviral treatment for human SARS-CoV-2, therefore identifying the drug treatment options as soon as possible is critical for the response to the COVID19 outbreak. Pro-inflammatory cascade and cytokine storm play a key role in the pathogenesis of new coronavirus. A large number of therapeutic interventions such as antiviral, antimalarial, convalescent plasma therapy, BCG vaccine, mTOR inhibitors, Tissue Plasminogen Activator, Human monoclonal antibodies, Anti-parasitic agents, Immunoenhancers, Nutritional interventions, JAK-STAT signaling inhibitors, ACE2 receptor modulators, and Angiotensin II receptor blockers have been either tried or suggested for effective treatment of patients with SARS-CoV-2 disease. Hence, we recommend that all the above potential interventions must be implemented in terms of their safety and efficacy through proper clinical experiments to control the emerging SARS-CoV-2 disease.
Keywords: SARS-CoV-2, ACE2 receptor modulators, cytokine storm, antimalarial, immunoenhancers, mTOR inhibitors, JAK-STAT signaling inhibitors.
[1] 
Center for Systems Science and Engineering (CSSE) at Johns Hopkins University.  Coronavirus 2019-nCoV. Available from: 
                    https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.,html#/bda7594740fd40299423467b48e9ecf6
[2] 
Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health  2020; 25(3): 278-80.
[http://dx.doi.org/10.1111/tmi.13383] [PMID: 32052514] 
[3] 
Phadke M, Saunik S. COVID-19 treatment by repurposing drugs until the vaccine is in sight. Drug Dev Res  2020; 81(5): 541-3.
[http://dx.doi.org/10.1002/ddr.21666] [PMID: 32227357] 
[4] 
Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci  2020; 248117477
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961] 
[5] 
Fauci AS, Lane HC, Redfield RR. Covid-19 - Navigating the uncharted. N Engl J Med  2020; 382(13): 1268-9.
[http://dx.doi.org/10.1056/NEJMe2002387] [PMID: 32109011] 
[6] 
Peeri NC, Shrestha N, Rahman MS, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int J Epidemiol  2020; 49(3): 717-26.
[http://dx.doi.org/10.1093/ije/dyaa033] [PMID: 32086938] 
[7] 
Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun  2020; 109102433
[http://dx.doi.org/10.1016/j.jaut.2020.102433] [PMID: 32113704] 
[8] 
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] 
[9] 
Ai T, Yang Z, Hou H, et al. Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases. Radiology  2020; 296(2): 41-5.
[http://dx.doi.org/10.1148/radiol.2020200642] [PMID: 32101510] 
[10] 
Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clin Med (Lond)  2020; 20(2): 124-7.
[http://dx.doi.org/10.7861/clinmed.2019-coron] [PMID: 32139372] 
[11] 
Cunningham AC, Goh HP, Koh D. Treatment of COVID-19: old tricks for new challenges. Crit Care  2020; 24(1): 91.
[http://dx.doi.org/10.1186/s13054-020-2818-6] [PMID: 32178711] 
[12] 
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] 
[13] 
Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res  2020; 7(1): 11.
[http://dx.doi.org/10.1186/s40779-020-00240-0] [PMID: 32169119] 
[14] 
Li H, Liu SM, Yu XH, Tang SL, Tang CK. Coronavirus disease 2019 (COVID-19): current status and future perspectives. Int J Antimicrob Agents  2020; 55(5)105951
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105951] [PMID: 32234466] 
[15] 
Liang T. Handbook of COVID-19 prevention and treatment. Hangzhou: Zhejiang University School of Medicine 2020.
[16] 
Watkins J. Preventing a covid-19 pandemic. British Med J  2020; 368: m810.
[http://dx.doi.org/10.1136/bmj.m810] 
[17] 
World Health Organization. Coronavirus disease 2019 (COVID19): situation report 2020. Available from:  
                    https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
[18] 
Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19) In: StatPearls StatPearls Publishing.  2020.
[19] 
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] 
[20] 
Habibzadeh P, Stoneman EK. The novel coronavirus: a bird’s eye view. Int J Occup Environ Med  2020; 11(2): 65-71.
[http://dx.doi.org/10.15171/ijoem.2020.1921] [PMID: 32020915] 
[21] 
Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends  2020; 14(1): 69-71.
[http://dx.doi.org/10.5582/bst.2020.01020] [PMID: 31996494] 
[22] 
Rabbi II. Current drugs with potential for treatment of COVID-19: a literature review. J Pharm Pharm Sci  2020; 23: 58-64.
[http://dx.doi.org/10.18433/jpps31002]] 
[23] 
Chen W-H, Hotez PJ, Bottazzi ME. Potential for developing a SARS-CoV receptor-binding domain (RBD) recombinant protein as a heterologous human vaccine against coronavirus infectious disease (COVID)-19. Hum Vaccin Immunother  2020; 16(6): 1239-42.
[http://dx.doi.org/10.1080/21645515.2020.1740560] [PMID: 32298218] 
[24] 
Hageman JR. The coronavirus disease 2019 (COVID-19). Pediatr Ann  2020; 49(3): e99-e100.
[http://dx.doi.org/10.3928/19382359-20200219-01] [PMID: 32155273] 
[25] 
Zhang R, Wang X, Ni L, et al. COVID-19: melatonin as a potential adjuvant treatment. Life Sci  2020; 250117583
[http://dx.doi.org/10.1016/j.lfs.2020.117583] [PMID: 32217117] 
[26] 
Chen C, Zhang XR, Ju ZY, He WF. Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies. Chin J Burns  2020; 36(6): 471-5.
[http://dx.doi.org/10.3760/cma.j.cn501120-20200224-00088.] 
[27] 
Vaninov N. In the eye of the COVID-19 cytokine storm. Nat Rev Immunol  2020; 20(5): 277.
[http://dx.doi.org/10.1038/s41577-020-0305-6] [PMID: 32249847] 
[28] 
Weaver LK, Behrens EM. Weathering the storm: improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis. Curr Treatm Opt Rheumatol  2017; 3(1): 33-48.
[http://dx.doi.org/10.1007/s40674-017-0059-x] [PMID: 28944163] 
[29] 
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents  2020; 55(5)105954
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105954] [PMID: 32234467] 
[30] 
Henderson LA, Canna SW, Schulert GS, et al. On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol  2020; 72(7): 1059-63.
[http://dx.doi.org/10.1002/art.41285] [PMID: 32293098] 
[31] 
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration. UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet  2020; 395(10229): 1033-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578] 
[32] 
Gerlach H. Agents to reduce cytokine storm. F1000 Res  2016; 5: 2909.
[http://dx.doi.org/10.12688/f1000research.9092.1] [PMID: 28105327] 
[33] 
Tveito K. Cytokine storms in COVID-19 cases? Tidsskrift for den
    Norske laegeforening: tidsskrift for praktisk medicin ny raekke 2020.
[34] 
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect  2020; 80(6): 607-13.
[http://dx.doi.org/10.1016/j.jinf.2020.03.037] 
[35] 
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect  2020; 9(1): 727-32.
[http://dx.doi.org/10.1080/22221751.2020.1746199] [PMID: 32196410] 
[36] 
Khalili JS, Zhu H, Mak NSA, Yan Y, Zhu Y. Novel coronavirus treatment with ribavirin: groundwork for an evaluation concerning COVID-19. J Med Virol  2020; 92(7): 740-6.
[http://dx.doi.org/10.1002/jmv.25798] [PMID: 32227493] 
[37] 
Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci  2020; 50(SI-1): 611-9.
[http://dx.doi.org/10.3906/sag-2004-145] [PMID: 32293834] 
[38] 
Bhatnagar T, Murhekar MV, Soneja M, et al. Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: protocol for restricted public health emergency use. Indian J Med Res  2020; 151(2 & 3): 184-9.
[PMID: 32362644] 
[39] 
Chen YW, Yiu CB, Wong KY. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000 Res  2020; 9: 129.
[http://dx.doi.org/10.12688/f1000research.22457.2] [PMID: 32194944] 
[40] 
Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol  2020; 92(6): 556-63.
[http://dx.doi.org/10.1002/jmv.25729] [PMID: 32104907] 
[41] 
Li H, Wang YM, Xu JY, Cao B. Potential antiviral therapeutics for 2019 novel coronavirus. Chin J Tuberculosis Respir Dis  2020; 43(3): 170-2.
[PMID: 32164080] 
[42] 
Roback JD, Guarner J. Convalescent plasma to treat COVID-19: possibilities and challenges. JAMA  2020; 323(16): 1561-2.
[http://dx.doi.org/10.1001/jama.2020.4940] [PMID: 32219429] 
[43] 
Bloch EM, Shoham S, Casadevall A, et al. Deployment of convalescent plasma for the prevention and treatment of COVID-19. J Clin Invest  2020; 130(6): 2757-65.
[http://dx.doi.org/10.1172/JCI138745] [PMID: 32254064] 
[44] 
Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis  2020; 20(4): 398-400.
[http://dx.doi.org/10.1016/S1473-3099(20)30141-9] [PMID: 32113510] 
[45] 
US Food and Drug Administration. Antibacterial Susceptibility Test Interpretive Criteria  Available from: 
                    https://www.fda.gov/drugs/development-resources/antibacterial-susceptibility-test-interpretive-criteria
[46] 
Shippey EA, Wagler VD, Collamer AN. Hydroxychloroquine: an old drug with new relevance. Cleve Clin J Med  2018; 85(6): 459-67.
[http://dx.doi.org/10.3949/ccjm.85a.17034] [PMID: 29883308] 
[47] 
Ruiz-Irastorza G, Khamashta M. Hydroxychloroquine: the cornerstone of lupus therapy. London: Sage Publications Sage UK 2008.
[48] 
Tanenbaum L, Tuffanelli DL. Antimalarial agents. Chloroquine, hydroxychloroquine, and quinacrine. Arch Dermatol  1980; 116(5): 587-91.
[http://dx.doi.org/10.1001/archderm.1980.01640290097026] [PMID: 6990871] 
[49] 
Ben-Zvi I, Kivity S, Langevitz P, Shoenfeld Y. Hydroxy-chloroquine: from malaria to autoimmunity. Clin Rev Allergy Immunol  2012; 42(2): 145-53.
[http://dx.doi.org/10.1007/s12016-010-8243-x] [PMID: 21221847] 
[50] 
Caminal-Montero L, Suárez-Díaz S. Hydroxychloroquine and antimalarials. J Rheumatol  2019; 46(11): 1547.
[http://dx.doi.org/10.3899/jrheum.190559] [PMID: 31308212] 
[51] 
Moore N. Chloroquine for COVID-19 infection. Drug Saf  2020; 43(5): 393-4.
[http://dx.doi.org/10.1007/s40264-020-00933-4] [PMID: 32266694] 
[52] 
Sharma OP. Effectiveness of chloroquine and hydroxychloroquine in treating selected patients with sarcoidosis with neurological involvement. Arch Neurol  1998; 55(9): 1248-54.
[http://dx.doi.org/10.1001/archneur.55.9.1248] [PMID: 9740120] 
[53] 
Gendrot M, Javelle E, Clerc A, Savini H, Pradines B, Pradines B. Chloroquine as a prophylactic agent against COVID-19? Int J Antimicrob Agents  2020; 55(6)105980
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105980] [PMID: 32294495] 
[54] 
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res  2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029] 
[55] 
Yao X, Ye F, Zhang M, et al. In Vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis  2020; 71(15)
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618] 
[56] 
Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents  2020; 55(5)105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740] 
[57] 
Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents  2007; 30(4): 297-308.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.05.015] [PMID: 17629679] 
[58] 
Chang R, Sun W-Z. Repositioning chloroquine as ideal antiviral prophylactic against COVID-19-time is now. Preprints  2020; 2020: 30279.
[http://dx.doi.org/10.20944/preprints202003.0279.v1] 
[59] 
Colson P, Rolain J-M, Raoult D. Chloroquine for the 2019 novel coronavirus SARS-CoV-2. Int J Antimicrob Agents  2020; 55(3)105923
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105923] [PMID: 32070753] 
[60] 
Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. Lancet Infect Dis  2006; 6(2): 67-9.
[http://dx.doi.org/10.1016/S1473-3099(06)70361-9] [PMID: 16439323] 
[61] 
Jie Z, He H, Xi H, Zhi Z. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Chin J
    Tuberculosis Respir Dis  2020; 43: 185-8.
[http://dx.doi.org/10.3760/cma.j.issn.1001-0939.2020.03.009] 
[62] 
Damle B, Vourvahis M, Wang E, Leaney J, Corrigan B. Clinical pharmacology perspectives on the antiviral activity of Azithromycin and use in COVID-19. Clin Pharmacol Ther  2020; 108(2): 201-11.
[http://dx.doi.org/10.1002/cpt.1857] [PMID: 32302411] 
[63] 
Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ  2020; 192(17): 450-3.
[http://dx.doi.org/10.1503/cmaj.200528]] 
[64] 
Sarma P, Kaur H, Kumar H, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis. J Med Virol  2020; 92(7): 776-85.
[http://dx.doi.org/10.1002/jmv.25898] [PMID: 32297988] 
[65] 
Gautret P, Lagier JC, Parola P, et al. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: a pilot observational study. Travel Med Infect Dis  2020; 34101663
[http://dx.doi.org/10.1016/j.tmaid.2020.101663] [PMID: 32289548] 
[66] 
Chen C-Y, Wang F-L, Lin C-C. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila)  2006; 44(2): 173-5.
[http://dx.doi.org/10.1080/15563650500514558] [PMID: 16615675] 
[67] 
Morgan ND, Patel SV, Dvorkina O. Suspected hydroxychloroquine-associated QT-interval prolongation in a patient with systemic lupus erythematosus. J Clin Rheumatol  2013; 19(5): 286-8.
[http://dx.doi.org/10.1097/RHU.0b013e31829d5e50] [PMID: 23872551] 
[68] 
Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204] 
[69] 
Yazdany J, Kim AHJ. Use of hydroxychloroquine and chloroquine during the COVID-19 pandemic: what every clinician should know. Ann Intern Med  2020; 172(11): 754-5.
[http://dx.doi.org/10.7326/M20-1334] [PMID: 32232419] 
[70] 
Kapoor A, Pandurangi U, Arora V, et al. Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: a scientific statement from the Indian Heart Rhythm Society. Indian Pacing Electrophysiol J  2020; 20(3): 117-20.
[http://dx.doi.org/10.1016/j.ipej.2020.04.003] [PMID: 32278018] 
[71] 
Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nat Med  2020; 26(6): 808-9.
[http://dx.doi.org/10.1038/s41591-020-0888-2] [PMID: 32488217] 
[72] 
Fan HH, Wang LQ, Liu WL, et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl)  2020; 133(9): 1051-6.
[http://dx.doi.org/10.1097/CM9.0000000000000797] 
[73] 
Miller A, Reandelar MJ, Fasciglione K, Roumenova V, Li Y, Otazu GH. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study. MedRxiv  2020; 2020: 1.
[http://dx.doi.org/10.1101/2020.03.24.20042937]] 
[74] 
Shet A, Ray D, Malavige N, Santosham M, Bar-Zeev N. Differential COVID-19-attributable mortality and BCG vaccine use in countries. MedRxiv  2020; 2020: 1.
[http://dx.doi.org/10.1101/2020.04.01.20049478]] 
[75] 
Kleinnijenhuis J, Quintin J, Preijers F, et al. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun  2014; 6(2): 152-8.
[http://dx.doi.org/10.1159/000355628] [PMID: 24192057] 
[76] 
Boer MC, Prins C, van Meijgaarden KE, van Dissel JT, Ottenhoff TH, Joosten SA. Mycobacterium bovis BCG vaccination induces divergent proinflammatory or regulatory T cell responses in adults. Clin Vaccine Immunol  2015; 22(7): 778-88.
[http://dx.doi.org/10.1128/CVI.00162-15] [PMID: 25947145] 
[77] 
Saban MR, Simpson C, Davis C, et al. Discriminators of mouse bladder response to intravesical Bacillus Calmette-Guerin (BCG). BMC Immunol  2007; 8: 6.
[http://dx.doi.org/10.1186/1471-2172-8-6] [PMID: 17506885] 
[78] 
Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ  2000; 321(7274): 1435-8.
[http://dx.doi.org/10.1136/bmj.321.7274.1435] [PMID: 11110734] 
[79] 
Salman S, Salem ML. The mystery behind childhood sparing by COVID-19. Int J Cancer Biomed Res  2020; 5(1): 11-3.
[http://dx.doi.org/10.21608/jcbr.2020.79888] 
[80] 
Dayal D, Gupta S. Connecting BCG vaccination and COVID-19: additional data. MedRxiv  2020; 2020: 1.
[http://dx.doi.org/10.1101/2020.04.07.20053272]] 
[81] 
Hegarty PK, Kamat AM, Zafirakis H, Dinardo A. BCG vaccination
    may be protective against COVID-19. Preprint 2020; 2020; 1
[http://dx.doi.org/10.13140/RG.2.2.35948.10880] 
[82] 
Zheng Y-F, Liu S-A. Prevent COVID-19 severity by repurposing mTOR inhibitors. Preprints  2020; 2020141258
[http://dx.doi.org/10.20944/preprints202004.0060.v1] 
[83] 
Ye L, Lee J, Xu L, et al. mTOR promotes antiviral humoral immunity by differentially regulating CD4 helper T cell and B cell responses. J Virol  2017; 91(4): 91.
[http://dx.doi.org/10.1128/JVI.01653-16] [PMID: 27974559] 
[84] 
Liu Y, Chan W, Wang Z, et al. Ontological and bioinformatic analysis of anti-coronavirus drugs and their implication for drug repurposing against COVID-19. Preprints  2020; 2020: 30413.
[http://dx.doi.org/10.20944/preprints202003.0413.v1] 
[85] 
Wang J, Hajizadeh N, Moore EE, et al. Tissue Plasminogen Activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost  2020; 18(7): 1752-5.
[http://dx.doi.org/10.1111/jth.14828] 
[86] 
Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. J Thromb Haemost  2020; 18(7): 1548-55.
[http://dx.doi.org/10.1111/jth.14872] [PMID: 32329246] 
[87] 
Laterre PF, Wittebole X, Dhainaut JF. Anticoagulant therapy in acute lung injury. Crit Care Med  2003; 31(4)(Suppl.): S329-36.
[http://dx.doi.org/10.1097/01.CCM.0000057912.71499.A5] [PMID: 12682461] 
[88] 
Moore HB, Barrett CD, Moore EE, et al. Is there a role for tissue plasminogen activator as a novel treatment for refractory COVID-19 associated acute respiratory distress syndrome? J Trauma Acute Care Surg  2020; 88(6): 1-2.
[http://dx.doi.org/10.1097/TA.0000000000002694] 
[89] 
Choudhury R, Barrett CD, Moore HB, et al. Salvage use of tissue plasminogen activator (tPA) in the setting of acute respiratory distress syndrome (ARDS) due to COVID-19 in the USA: a Markov decision analysis. World J Emerg Surg  2020; 15(1): 29.
[http://dx.doi.org/10.1186/s13017-020-00305-4] [PMID: 32312290] 
[90] 
Kaur S, Bansal Y, Kumar R, Bansal G. A panoramic review of IL-6: structure, pathophysiological roles and inhibitors. Bioorg Med Chem  2020; 28(5)115327
[http://dx.doi.org/10.1016/j.bmc.2020.115327] [PMID: 31992476] 
[91] 
Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood  2008; 112(10): 3959-64.
[http://dx.doi.org/10.1182/blood-2008-05-155846] [PMID: 18784373] 
[92] 
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol  2020; 92(7): 814-8.
[http://dx.doi.org/10.1002/jmv.25801] [PMID: 32253759] 
[93] 
Wang C, Li W, Drabek D, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun  2020; 2020: 2251.
[http://dx.doi.org/10.1038/s41467-020-16256-y]] 
[94] 
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res  2020; 178104787
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768] 
[95] 
Raniga K, Liang C. Interferons: reprogramming the metabolic network against viral infection. Viruses  2018; 10(1): 10.
[http://dx.doi.org/10.3390/v10010036] [PMID: 29342871] 
[96] 
Lu CC, Chen MY, Chang YL. Potential therapeutic agents against COVID-19: what we know so far. J Chin Med Assoc  2020; 83(6): 534-6.
[http://dx.doi.org/10.1097/JCMA.0000000000000318.] 
[97] 
Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun  2020; 11(1): 222.
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID: 31924756] 
[98] 
Ströher U, DiCaro A, Li Y, et al. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha. J Infect Dis  2004; 189(7): 1164-7.
[http://dx.doi.org/10.1086/382597] [PMID: 15031783] 
[99] 
Villamor E, Mbise R, Spiegelman D, et al. Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics  2002; 109(1)E6
[http://dx.doi.org/10.1542/peds.109.1.e6] [PMID: 11773574] 
[100] 
Jee J, Hoet AE, Azevedo MP, et al. Effects of dietary vitamin A content on antibody responses of feedlot calves inoculated intramuscularly with an inactivated bovine coronavirus vaccine. Am J Vet Res  2013; 74(10): 1353-62.
[http://dx.doi.org/10.2460/ajvr.74.10.1353] [PMID: 24066921] 
[101] 
Hemilä H. Vitamin C intake and susceptibility to pneumonia. Pediatr Infect Dis J  1997; 16(9): 836-7.
[http://dx.doi.org/10.1097/00006454-199709000-00003] [PMID: 9306475] 
[102] 
Carlberg C, Vitamin D. Vitamin D signaling in the context of innate immunity: focus on human monocytes. Front Immunol  2019; 10: 2211.
[http://dx.doi.org/10.3389/fimmu.2019.02211] [PMID: 31572402] 
[103] 
Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients  2020; 12(4): 988.
[104] 
Jakovac H. COVID-19 and vitamin D-Is there a link and an opportunity for intervention? Am J Physiol Endocrinol Metab  2020; 318(5)E589
[http://dx.doi.org/10.1152/ajpendo.00138.2020] [PMID: 32297519] 
[105] 
Qian F, Misra S, Prabhu KS. Selenium and selenoproteins in prostanoid metabolism and immunity. Crit Rev Biochem Mol Biol  2019; 54(6): 484-516.
[http://dx.doi.org/10.1080/10409238.2020.1717430] [PMID: 31996052] 
[106] 
Guillin OM, Vindry C, Ohlmann T, Chavatte L. Selenium, Selenoproteins and viral infection. Nutrients  2019; 11(9): 11.
[http://dx.doi.org/10.3390/nu11092101] [PMID: 31487871] 
[107] 
Lee MO, Cho YS. The role of selenium-mediated redox signaling by selenophosphate synthetase 1 (SEPHS1) in hESCs. Biochem Biophys Res Commun  2019; 520(2): 406-12.
[http://dx.doi.org/10.1016/j.bbrc.2019.09.123] [PMID: 31607477] 
[108] 
Spengler G, Kincses A, Mosolygó T, et al. Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides. Molecules  2019; 24(23): 24.
[http://dx.doi.org/10.3390/molecules24234264] [PMID: 31771095] 
[109] 
Zhang L, Liu Y. Potential interventions for novel coronavirus in China: a systematic review. J Med Virol  2020; 92(5): 479-90.
[http://dx.doi.org/10.1002/jmv.25707] [PMID: 32052466] 
[110] 
Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The role of zinc in
    antiviral immunity advances in nutrition (Bethesda, Md) 2019; 10: 696-710.
[http://dx.doi.org/10.1093/advances/nmz013] 
[111] 
Skalny AV, Rink L, Ajsuvakova OP, et al. Zinc and respiratory tract infections: perspectives for COVID 19. [review] Int J Mol Med  2020; 46(1): 17-26.
[PMID: 32319538] 
[112] 
Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med  2020; 46(4): 586-90.
[http://dx.doi.org/10.1007/s00134-020-05985-9] [PMID: 32125455] 
[113] 
Takahashi S, Yoshiya T, Yoshizawa-Kumagaye K, Sugiyama T. Nicotianamine is a novel angiotensin-converting enzyme 2 inhibitor in soybean. Biomed Res  2015; 36(3): 219-24.
[http://dx.doi.org/10.2220/biomedres.36.219] [PMID: 26106051] 
[114] 
Cheng L, Zheng W, Li M, et al. Citrus fruits are rich in flavonoids for immunoregulation and potential targeting ACE2. Preprints  2020; 2020: 20313.
[115] 
Lin C-W, Tsai F-J, Tsai C-H, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res  2005; 68(1): 36-42.
[http://dx.doi.org/10.1016/j.antiviral.2005.07.002] [PMID: 16115693] 
[116] 
Kruse RL. Therapeutic strategies in an outbreak scenario to treat the novel coronavirus originating in Wuhan, China. F1000 Res  2020; 9: 72.
[http://dx.doi.org/10.12688/f1000research.22211.2] [PMID: 32117569] 
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DOI https://dx.doi.org/10.2174/2666796701999200721003212	Print ISSN 2666-7967
Publisher Name Bentham Science Publisher	Online ISSN 2666-7975
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