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Therapeutic Candidates for COVID-19: A Comprehensive Review of Antiviral, Immunomodulatory, and Emerging Treatments

Document Type : Original Article

Author

Department of Anasthesiology, School of Medicine, Alborz University of Medical Science, Karaj, Iran.

Abstract
Background and Objectives:
The coronavirus first appeared in Wuhan, China, in late November 2019, and has since spread to more than one hundred countries. COVID-19 has been declared by the World Health Organization as a Public Health Emergency of International Interest. This has been the result of a virus now having reached pandemic proportions and there not being an effective vaccine or antiviral treatment. In this article, we aim to highlight each current drug being tested for potential effectiveness on this disease.
Methodology: The research is a descriptive review conducted by a search in reputable scientific databases, including Scopus, Google Scholar, and PubMed, utilizing the phrases virus, coronavirus, COVID-19, SARS-CoV-2, and treatment. The latest expertise:given that the development and efficacy of antiviral drugs require substantial time, monotherapy for other diseases may represent the most efficient therapeutic option for a certain condition. Pharmaceuticals with broad-spectrum efficacy, including Bevacizumab, Methylprednisolone, Fingolimod, fluoxetine, Ritonavir, chloroquine Fesnate, remdesivir, and Favipiravir, are currently under investigation as prospective candidates in various clinical trials.
Conclusion: To conclude, all these drugs are potentially useful in the prevention and treatment of diseases. But none of these drugs is a cure-all, specific treatment for COVID-19. Therefore, we must continue to search for an effective drug treatment for this disease until we have a proven successful agent available.

Keywords

Subjects


1.Chauhan S. Comprehensive review of coronavirus disease 2019 (COVID-19). Biomedical journal. 2020;43(4):334-40.
2.Sturrock BR, Chevassut TJ. Chloroquine and COVID-19 - a potential game changer? Clinical medicine (London, England). 2020;20(3):278-81.
3.Pardi N, Weissman D. Development of vaccines and antivirals for combating viral pandemics. Nature biomedical engineering. 2020;4(12):1128-33.
4.Goyal R, Gautam RK, Chopra H, Dubey AK, Singla RK, Rayan RA, et al. Comparative highlights on MERS-CoV, SARS-CoV-1, SARS-CoV-2, and NEO-CoV. EXCLI journal. 2022;21:1245-72.
5.Baker SA, Kwok S, Berry GJ, Montine TJ. Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation. PloS one. 2021;16(2):e0247060.
6.Zandi M, Soltani S, Feyzi K. SARS-CoV-2 as a betacoronavirus comprises five structural proteins? Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2021;94:105011.
7.Abdelrahman Z, Li M, Wang X. Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses. 2020;11.
8.Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon. 2023;9(2):e13323.
9.Beutels P, Scuffham PA, MacIntyre CR. Funding of drugs: do vaccines warrant a different approach? The Lancet Infectious diseases. 2008;8(11):727-33.
10.Lei ZN, Wu ZX, Dong S, Yang DH, Zhang L, Ke Z, et al. Chloroquine and hydroxychloroquine in the treatment of malaria and repurposing in treating COVID-19. Pharmacology & therapeutics. 2020;216:107672.
11.Al-Horani RA, Kar S, Aliter KF. Potential Anti-COVID-19 Therapeutics that Block the Early Stage of the Viral Life Cycle: Structures, Mechanisms, and Clinical Trials. International journal of molecular sciences. 2020;21(15).
12.Liu X, Chen H, Shang Y, Zhu H, Chen G, Chen Y, et al. Efficacy of chloroquine versus lopinavir/ritonavir in mild/general COVID-19 infection: a prospective, open-label, multicenter, randomized controlled clinical study. Trials. 2020;21(1):622.
13.Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nature reviews Microbiology. 2021;19(3):141-54.
14.He X, Cheng X, Feng X, Wan H, Chen S, Xiong M. Clinical Symptom Differences Between Mild and Severe COVID-19 Patients in China: A Meta-Analysis. Frontiers in public health. 2020;8:561264.
15.Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nature reviews Disease primers. 2019;5(1):18.
16.Raghav PK, Mann Z, Ahluwalia SK, Rajalingam R. Potential treatments of COVID-19: Drug repurposing and therapeutic interventions. Journal of Pharmacological Sciences. 2023;152(1):1-21.
17.Bastani P, Dehghan Z, Kashfi SM, Dorosti H, Mohammadpour M, Mehralian G. Challenge of Politico-Economic Sanctions on Pharmaceutical Procurement in Iran: A Qualitative Study %J Iranian Journal of Medical Sciences. 2022;47(2):152-61.
18.Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, et al. Stem cell-based therapy for human diseases. Signal transduction and targeted therapy. 2022;7(1):272.
19.Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik YS, et al. Coronavirus Disease 2019-COVID-19. Clinical microbiology reviews. 2020;33(4).
20.Singh R, Singh PK, Kumar R, Kabir MT, Kamal MA, Rauf A, et al. Multi-Omics Approach in the Identification of Potential Therapeutic Biomolecule for COVID-19. Frontiers in pharmacology. 2021;12:652335.
21.Deng J, Zhou F, Hou W, Heybati K, Ali S, Chang O, et al. Efficacy of lopinavir-ritonavir combination therapy for the treatment of hospitalized COVID-19 patients: a meta-analysis. Future virology. 2021.
22.Hemida MG. The next-generation coronavirus diagnostic techniques with particular emphasis on the SARS-CoV-2. Journal of medical virology. 2021;93(7):4219-41.
23.Josuttis D, Schwedler C, Heymann G, Gümbel D, Schmittner MD, Kruse M, et al. Vascular Endothelial Growth Factor as Potential Biomarker for COVID-19 Severity. Journal of intensive care medicine. 2023;38(12):1165-73.
24.Hernandez-Pacheco N, Guillen-Guio B, Acosta-Herrera M, Pino-Yanes M, Corrales A, Ambrós A, et al. A vascular endothelial growth factor receptor gene variant is associated with susceptibility to acute respiratory distress syndrome. Intensive Care Medicine Experimental. 2018;6(1):16.
25.Wang Z, Li J, Guo J, Wei P. Direct antitumor activity of bevacizumab: an overlooked mechanism? Frontiers in pharmacology. 2024;15.
26.Chia S, Tay SJ, Song Z, Yang Y, Walsh I, Pang KT. Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content. Biomedicine & Pharmacotherapy. 2023;163:114757.
27.Horie S, McNicholas B, Rezoagli E, Pham T, Curley G, McAuley D, et al. Emerging pharmacological therapies for ARDS: COVID-19 and beyond. Intensive care medicine. 2020;46(12):2265-83.
28.Wang Z, Li J, Guo J, Wei P. Direct antitumor activity of bevacizumab: an overlooked mechanism? 2024;15.
29.Téllez Arévalo AM, Quaye A, Rojas-Rodríguez LC, Poole BD, Baracaldo-Santamaría D, Tellez Freitas CM. Synthetic Pharmacotherapy for Systemic Lupus Erythematosus: Potential Mechanisms of Action, Efficacy, and Safety. Medicina [Internet]. 2023; 59(1).
30.Jones KF, Merlin JS. Approaches to opioid prescribing in cancer survivors: Lessons learned from the general literature. Cancer. 2022;128(3):449-55.
31.Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? International journal of antimicrobial agents. 2020;55(5):105938.
32.Rosa SGV, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Revista panamericana de salud publica = Pan American journal of public health. 2020;44:e40.
33.Pruijssers AJ, George AS, Schäfer A, Leist SR, Gralinksi LE, Dinnon KH, 3rd, et al. Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice. Cell reports. 2020;32(3):107940.
34.Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. The Journal of biological chemistry. 2020;295(20):6785-97.
35.Chen J, Dai L, Kendrick S, Post SR, Qin Z. The Anti-COVID-19 Drug Remdesivir Promotes Oncogenic Herpesvirus Reactivation through Regulation of Intracellular Signaling Pathways. Antimicrobial agents and chemotherapy. 2022;66(3):e0239521.
36.Vermillion MS, Murakami E, Ma B, Pitts J, Tomkinson A, Rautiola D, et al. Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection. Science translational medicine. 2022;14(633):eabl8282.
37.Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell research. 2020;30(3):269-71.
38.Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. International journal of antimicrobial agents. 2020;55(5):105955.
39.Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral research. 2013;100(2):446-54.
40.Konstantinova ID, V LA, Fateev IV, Esipov RS. Favipiravir and Its Structural Analogs: Antiviral Activity and Synthesis Methods. Acta naturae. 2022;14(2):16-38.
41.Chang Y-C, Tung Y-A, Lee K-H, Chen T-F, Hsiao Y-C, Chang H-C, et al. Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking. Preprintsorg. 2020.
42.Grundeis F, Ansems K, Dahms K, Thieme V, Metzendorf MI, Skoetz N, et al. Remdesivir for the treatment of COVID-19. The Cochrane database of systematic reviews. 2023;1(1):Cd014962.
43.Labhardt ND, Smit M, Petignat I, Perneger T, Marinosci A, Ustero P, et al. Post-exposure Lopinavir-Ritonavir Prophylaxis versus Surveillance for Individuals Exposed to SARS-CoV-2: The COPEP Pragmatic Open-Label, Cluster Randomized Trial. EClinicalMedicine. 2021;42:101188.
44.Singh M, de Wit E. Antiviral agents for the treatment of COVID-19: Progress and challenges. Cell reports Medicine. 2022;3(3):100549.
45.Zhang J, Xie B, Hashimoto K. Current status of potential therapeutic candidates for the COVID-19 crisis. Brain, behavior, and immunity. 2020;87:59-73.
46.Idda ML, Soru D, Floris M. Overview of the First 6 Months of Clinical Trials for COVID-19 Pharmacotherapy: The Most Studied Drugs. Frontiers in public health. 2020;8:497.
47.Yeung K, Qiao W, Lau HE, Xie HZ, Poon V, Chan C, et al. SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters. Research Square. 2021.
48.Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. The New England journal of medicine. 2012;367(19):1814-20.
49.Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. The New England journal of medicine. 2020;382(8):727-33.
50.Filip R, Gheorghita Puscaselu R, Anchidin-Norocel L, Dimian M, Savage WK. Global Challenges to Public Health Care Systems during the COVID-19 Pandemic: A Review of Pandemic Measures and Problems. Journal of personalized medicine. 2022;12(8).
51.Shyr ZA, Cheng YS, Lo DC, Zheng W. Drug combination therapy for emerging viral diseases. Drug discovery today. 2021;26(10):2367-76.
52.Nguyen HL, Thai NQ, Truong DT, Li MS. Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations. The Journal of Physical Chemistry B. 2020;124(50):11337-48.
53.Nguyen HL, Thai NQ, Truong DT, Li MS. Remdesivir Strongly Binds to Both RNA-Dependent RNA Polymerase and Main Protease of SARS-CoV-2: Evidence from Molecular Simulations. The journal of physical chemistry B. 2020;124(50):11337-48.
54.Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, et al. Efficacy and Safety of Lopinavir/Ritonavir or Arbidol in Adult Patients with Mild/Moderate COVID-19: An Exploratory Randomized Controlled Trial. Med (New York, NY). 2020;1(1):105-13.e4.
55.Smolders EJ, Te Brake LH, Burger DM. SARS-CoV-2 and HIV protease inhibitors: why lopinavir/ritonavir will not work for COVID-19 infection. Antiviral therapy. 2020;25(7):345-7.
56.Adeshina YO, Deeds EJ, Karanicolas J. Machine learning classification can reduce false positives in structure-based virtual screening. Proceedings of the National Academy of Sciences of the United States of America. 2020;117(31):18477-88.
57.Das A, Roy S, Swarnakar S, Chatterjee N. Understanding the immunological aspects of SARS-CoV-2 causing COVID-19 pandemic: A therapeutic approach. Clinical immunology (Orlando, Fla). 2021;231:108804.
58.Baldelli S, Corbellino M, Clementi E, Cattaneo D, Gervasoni C. Lopinavir/ritonavir in COVID-19 patients: maybe yes, but at what dose? The Journal of antimicrobial chemotherapy. 2020;75(9):2704-6.
Volume 10, Issue 36 - Serial Number 36
Original article
Winter 2025
Pages 12-18

  • Receive Date 30 October 2024
  • Revise Date 29 December 2024
  • Accept Date 17 February 2025