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Infectious Disorders - Drug Targets

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ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

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Research Article

Two Birds with One Stone: Drug Regime Targets Viral Pathogenesis Phases and COVID-19 ARDS at the Same Time

Author(s): Ghazaleh Ghavami and Soroush Sardari*

Volume 24, Issue 8, 2024

Published on: 29 January, 2024

Article ID: e290124226467 Pages: 14

DOI: 10.2174/0118715265270637240107153121

Price: $65

Abstract

Background: Severe COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a kind of viral pneumonia induced by infection with the coronavirus that causes ARDS. It involves symptoms that are a combination of viral pneumonia and ARDS. Antiviral or immunosuppressive medicines are used to treat many COVID-19 patients. Several drugs are now undergoing clinical studies in order to see if they can be repurposed in the future.

Material and Methods: In this study, in silico biomarker-targeted methodologies, such as target/ molecule virtual screening by docking technique and drug repositioning strategy, as well as data mining approach and meta-analysis of investigational data, were used.

Results: In silico findings of used combination of drug repurposing and high-throughput docking methods presented acetaminophen, ursodiol, and β-carotene as a three-drug therapy regimen to treat ARDS induced by viral pneumonia in addition to inducing direct antiviral effects against COVID-19 viral infection.

Conclusion: In the current study, drug repurposing and high throughput docking methods have been employed to develop combination drug regimens as multiple-molecule drugs for the therapy of COVID-19 and ARDS based on a multiple-target therapy strategy. This approach offers a promising avenue for the treatment of COVID-19 and ARDS, and highlights the potential benefits of drug repurposing in the fight against the current pandemic.

Graphical Abstract

[1]
Long B, Carius BM, Chavez S, et al. Clinical update on COVID-19 for the emergency clinician: Presentation and evaluation. Am J Emerg Med 2022; 54: 46-57.
[http://dx.doi.org/10.1016/j.ajem.2022.01.028] [PMID: 35121478]
[2]
Zoumpourlis V, Goulielmaki M, Rizos E, Baliou S, Spandidos D. The COVID 19 pandemic as a scientific and social challenge in the 21st century. Mol Med Rep 2020; 22(4): 3035-48.
[http://dx.doi.org/10.3892/mmr.2020.11393] [PMID: 32945405]
[3]
Our World In Data Coronavirus Pandemic (COVID-19). 2023. Available From: https://ourworldindata.org/coronavirus
[4]
Gibson PG, Qin L, Puah SH. COVID ‐19 acute respiratory distress syndrome (ARDS): Clinical features and differences from typical pre‐ COVID ‐19 ARDS. Med J Aust 2020; 213(2): 54-56.e1.
[http://dx.doi.org/10.5694/mja2.50674] [PMID: 32572965]
[5]
Badraoui R, Alrashedi MM, El-May MV, Bardakci F. Acute respiratory distress syndrome: A life threatening associated complication of SARS-CoV-2 infection inducing COVID-19. J Biomol Struct Dyn 2020; 5: 1-10.
[http://dx.doi.org/10.1080/07391102.2020.1803139] [PMID: 32752936]
[6]
Ferrari F, Martins VM, Teixeira M, Santos RD, Stein R. COVID-19 and Thromboinflammation: Is There a Role for Statins? Clinics (São Paulo) 2021; 76: e2518.
[http://dx.doi.org/10.6061/clinics/2021/e2518] [PMID: 33787678]
[7]
Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S. Trifirٍ G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol 2020; 11: 588654.
[http://dx.doi.org/10.3389/fphar.2020.588654] [PMID: 33240091]
[8]
Low ZY, Farouk IA, Lal SK. Drug Repositioning: New Approaches and Future Prospects for Life-Debilitating Diseases and the COVID-19 Pandemic Outbreak. Viruses 2020; 12(9): 1058.
[http://dx.doi.org/10.3390/v12091058] [PMID: 32972027]
[9]
Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: A narrative review. Postgrad Med 2011; 123(5): 194-204.
[http://dx.doi.org/10.3810/pgm.2011.09.2475] [PMID: 21904102]
[10]
Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemp Clin Trials Commun 2018; 11: 156-64.
[http://dx.doi.org/10.1016/j.conctc.2018.08.001] [PMID: 30112460]
[11]
Wong NA, Saier MH Jr. The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis. Int J Mol Sci 2021; 22(3): 1308.
[http://dx.doi.org/10.3390/ijms22031308] [PMID: 33525632]
[12]
Yang G, Tan Z, Zhou L, et al. Effects of angiotensin II receptor blockers and ACE (Angiotensin-Converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: A single-center retrospective study. Hypertension 2020; 76(1): 51-8.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15143] [PMID: 32348166]
[13]
Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382(18): 1708-20.
[http://dx.doi.org/10.1056/NEJMoa2002032] [PMID: 32109013]
[14]
Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J Microbiol Immunol Infect 2020; 53(3): 436-43.
[http://dx.doi.org/10.1016/j.jmii.2020.03.034] [PMID: 32307245]
[15]
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323(13): 1239-42.
[http://dx.doi.org/10.1001/jama.2020.2648] [PMID: 32091533]
[16]
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18(5): 1094-9.
[http://dx.doi.org/10.1111/jth.14817] [PMID: 32220112]
[17]
Batra N, De Souza C, Batra J, Raetz AG, Yu AM. The HMOX1 Pathway as a Promising Target for the Treatment and Prevention of SARS-CoV-2 of 2019 (COVID-19). Int J Mol Sci 2020; 21(17): 6412.
[http://dx.doi.org/10.3390/ijms21176412] [PMID: 32899231]
[18]
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C. Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev 2020; 54: 62-75.
[http://dx.doi.org/10.1016/j.cytogfr.2020.06.001]
[19]
Liu Y, Yao W, Xu J, et al. The anti-inflammatory effects of acetaminophen and N -acetylcysteine through suppression of the NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes. Innate Immun 2015; 21(6): 587-97.
[http://dx.doi.org/10.1177/1753425914566205] [PMID: 25575547]
[20]
Lin L, Xu L, Lv W, et al. An NLRP3 inflammasome-triggered cytokine storm contributes to Streptococcal toxic shock-like syndrome (STSLS). PLoS Pathog 2019; 15(6): e1007795.
[http://dx.doi.org/10.1371/journal.ppat.1007795] [PMID: 31170267]
[21]
Simmons DL, Wagner D, Westover K. Nonsteroidal anti-inflammatory drugs, acetaminophen, cyclooxygenase 2, and fever. Clin Infect Dis 2000; 31 (Suppl. 5): S211-8.
[http://dx.doi.org/10.1086/317517] [PMID: 11113025]
[22]
Kwon MS, Shim EJ, Seo YJ, et al. Effect of aspirin and acetaminophen on proinflammatory cytokine-induced pain behavior in mice. Pharmacology 2005; 74(3): 152-6.
[http://dx.doi.org/10.1159/000084548] [PMID: 15775706]
[23]
Matthay MA, Zemans RL, Zimmerman GA, et al. Acute respiratory distress syndrome. Nat Rev Dis Primers 2019; 5(1): 18.
[http://dx.doi.org/10.1038/s41572-019-0069-0] [PMID: 30872586]
[24]
Janz DR, Bastarache JA, Rice TW, et al. Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: The Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial. Crit Care Med 2015; 43(3): 534-41.
[http://dx.doi.org/10.1097/CCM.0000000000000718] [PMID: 25474535]
[25]
Zhao WX, Zhang JH, Cao JB, et al. Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity. J Neuroinflammation 2017; 14(1): 17.
[http://dx.doi.org/10.1186/s12974-016-0781-6] [PMID: 28109286]
[26]
Yoshikawa M, Tsujii T, Matsumura K, et al. Immunomodulatory effects of ursodeoxycholic acid on immune responses. Hepatology 1992; 16(2): 358-64.
[http://dx.doi.org/10.1002/hep.1840160213] [PMID: 1639344]
[27]
Ishizaki K, Iwaki T, Kinoshita S, et al. Ursodeoxycholic acid protects concanavalin A-induced mouse liver injury through inhibition of intrahepatic tumor necrosis factor-α and macrophage inflammatory protein-2 production. Eur J Pharmacol 2008; 578(1): 57-64.
[http://dx.doi.org/10.1016/j.ejphar.2007.08.031] [PMID: 17888421]
[28]
Manousou P, Kolios G, Drygiannakis I, et al. CXCR3 axis in patients with primary biliary cirrhosis: A possible novel mechanism of the effect of ursodeoxycholic acid. Clin Exp Immunol 2013; 172(1): 9-15.
[http://dx.doi.org/10.1111/cei.12032] [PMID: 23480180]
[29]
Ko WK, Lee SH, Kim SJ, et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PLoS One 2017; 12(6): e0180673.
[http://dx.doi.org/10.1371/journal.pone.0180673] [PMID: 28665991]
[30]
Niu F, Li H, Xu X, Sun L, Gan N, Wang A. Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome. J Cell Mol Med 2020; 24(24): 14626-32.
[http://dx.doi.org/10.1111/jcmm.15985] [PMID: 33145933]
[31]
García-Romero CS, Guzman C, Cervantes A, Cerbón M. Liver disease in pregnancy: Medical aspects and their implications for mother and child. Ann Hepatol 2019; 18(4): 553-62.
[http://dx.doi.org/10.1016/j.aohep.2019.04.009] [PMID: 31126882]
[32]
Kawata A, Murakami Y, Suzuki S, Fujisawa S. Anti-inflammatory Activity of β-Carotene, Lycopene and Tri-n-butylborane, a Scavenger of Reactive Oxygen Species. In Vivo 2018; 32(2): 255-64.
[http://dx.doi.org/10.21873/invivo.11232] [PMID: 29475907]
[33]
Thakor TR, Lo WA. Competition and R&D Financing: Evidence from the Biopharmaceutical Industry. SSRN Elec J 2020 2020; 85
[http://dx.doi.org/10.2139/ssrn.3754494]
[34]
Araz O. Current Pharmacological Approach to ARDS: The Place of Bosentan. Eurasian J Med 2020; 52(1): 81-5.
[http://dx.doi.org/10.5152/eurasianjmed.2020.19218] [PMID: 32158321]

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