COVID-19 Therapeutics

Overview

Journal Clin Microbiol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 2024 May 21

PMID 38771027

Authors

Daniele Focosi

Massimo Franchini

Fabrizio Maggi

Shmuel Shoham

Affiliations

Soon will be listed here.

Abstract

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range of therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy of those approaches often remains controversial or compromised by viral evolution. Uncertainties still persist regarding the best therapies for high-risk patients, and the drug pipeline is suffering fatigue and shortage of funding. In this article, we review the antiviral activity, mechanism of action, pharmacokinetics, and safety of COVID-19 antiviral therapies. Additionally, we summarize the evidence from randomized controlled trials on efficacy and safety of the various COVID-19 antivirals and discuss unmet needs which should be addressed.

Citing Articles

Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications.

Luo Y, Huang A, Tang K World J Gastroenterol. 2025; 31(6):100864.

PMID: 39958440 PMC: 11752700. DOI: 10.3748/wjg.v31.i6.100864.

SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development.

Angius F, Puxeddu S, Zaimi S, Canton S, Nematollahzadeh S, Pibiri A Vaccines (Basel). 2025; 13(1).

PMID: 39852796 PMC: 11769326. DOI: 10.3390/vaccines13010017.

Backstage Heroes-Yeast in COVID-19 Research.

Grabinski W, Karachitos A, Kicinska A Int J Mol Sci. 2024; 25(23.

PMID: 39684373 PMC: 11640846. DOI: 10.3390/ijms252312661.

Limited Short-Term Evolution of SARS-CoV-2 RNA-Dependent RNA Polymerase under Remdesivir Exposure in Upper Respiratory Compartments.

Novitsky V, Beckwith C, Carpenter-Azevedo K, Shin J, Hague J, Sam S Viruses. 2024; 16(10).

PMID: 39459846 PMC: 11512361. DOI: 10.3390/v16101511.

Does early combination vs. Monotherapy improve clinical outcomes of clinically extremely vulnerable patients with COVID-19? Results from a retrospective propensity-weighted analysis.

Maria M, Maraolo A, Cozzolino C, Sasset L, Ferrari A, Basso M Eur J Med Res. 2024; 29(1):484.

PMID: 39367485 PMC: 11451216. DOI: 10.1186/s40001-024-02062-5.

References

Sasi V, Ullrich S, Ton J, Fry S, Johansen-Leete J, Payne R . Predicting Antiviral Resistance Mutations in SARS-CoV-2 Main Protease with Computational and Experimental Screening. Biochemistry. 2022; 61(22):2495-2505. DOI: 10.1021/acs.biochem.2c00489. View

Dai W, Zhang B, Jiang X, Su H, Li J, Zhao Y . Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020; 368(6497):1331-1335. PMC: 7179937. DOI: 10.1126/science.abb4489. View

Hueso T, Godron A, Lanoy E, Pacanowski J, Levi L, Gras E . Convalescent plasma improves overall survival in patients with B-cell lymphoid malignancy and COVID-19: a longitudinal cohort and propensity score analysis. Leukemia. 2022; 36(4):1025-1034. PMC: 8805670. DOI: 10.1038/s41375-022-01511-6. View

Hansen J, Baum A, Pascal K, Russo V, Giordano S, Wloga E . Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science. 2020; 369(6506):1010-1014. PMC: 7299284. DOI: 10.1126/science.abd0827. View

Rosenke K, Okumura A, Lewis M, Feldmann F, Meade-White K, Bohler W . Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model. JCI Insight. 2022; 7(13). PMC: 9310535. DOI: 10.1172/jci.insight.160108. View

Abdelnabi R, Foo C, Jochmans D, Vangeel L, De Jonghe S, Augustijns P . The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. Nat Commun. 2022; 13(1):719. PMC: 8847371. DOI: 10.1038/s41467-022-28354-0. View

Cox R, Lieber C, Wolf J, Karimi A, Lieberman N, Sticher Z . Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models. Nat Commun. 2023; 14(1):4731. PMC: 10406822. DOI: 10.1038/s41467-023-40556-8. View

Gordon A, Mouncey P, Al-Beidh F, Rowan K, Nichol A, Arabi Y . Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021; 384(16):1491-1502. PMC: 7953461. DOI: 10.1056/NEJMoa2100433. View

Painter G, Natchus M, Cohen O, Holman W, Painter W . Developing a direct acting, orally available antiviral agent in a pandemic: the evolution of molnupiravir as a potential treatment for COVID-19. Curr Opin Virol. 2021; 50:17-22. PMC: 8277160. DOI: 10.1016/j.coviro.2021.06.003. View

10.

Rodrigues C, Freitas-Santos R, Levi J, Senerchia A, Lopes A, Santos S . Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in an outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance. Int J Antimicrob Agents. 2021; 58(5):106428. PMC: 8386096. DOI: 10.1016/j.ijantimicag.2021.106428. View

11.

Jagannathan P, Andrews J, Bonilla H, Hedlin H, Jacobson K, Balasubramanian V . Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun. 2021; 12(1):1967. PMC: 8009873. DOI: 10.1038/s41467-021-22177-1. View

12.

Lenze E, Mattar C, Zorumski C, Stevens A, Schweiger J, Nicol G . Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324(22):2292-2300. PMC: 7662481. DOI: 10.1001/jama.2020.22760. View

13.

Malin J, Suarez I, Priesner V, Fatkenheuer G, Rybniker J . Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev. 2020; 34(1). PMC: 7566896. DOI: 10.1128/CMR.00162-20. View

14.

Troseid M, Arribas J, Assoumou L, Holten A, Poissy J, Terzic V . Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial. Crit Care. 2023; 27(1):9. PMC: 9830601. DOI: 10.1186/s13054-022-04205-8. View

15.

Welen K, Rosendal E, Gisslen M, Lenman A, Freyhult E, Fonseca-Rodriguez O . A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data. Eur Urol. 2022; 81(3):285-293. PMC: 8673828. DOI: 10.1016/j.eururo.2021.12.013. View

16.

Fenwick C, Turelli P, Ni D, Perez L, Lau K, Herate C . Patient-derived monoclonal antibody neutralizes SARS-CoV-2 Omicron variants and confers full protection in monkeys. Nat Microbiol. 2022; 7(9):1376-1389. PMC: 9418005. DOI: 10.1038/s41564-022-01198-6. View

17.

Nakamura K, Fujimoto K, Hasegawa C, Aoki I, Yoshitsugu H, Ugai H . A phase I, randomized, placebo-controlled study of molnupiravir in healthy Japanese to support special approval in Japan to treat COVID-19. Clin Transl Sci. 2022; 15(11):2697-2708. PMC: 9538808. DOI: 10.1111/cts.13395. View

18.

Chang C, Peng W, Lee W, Lin T, Yang M, Dalley J . Transfer and biotransformation of the COVID-19 prodrug molnupiravir and its metabolite β-D-N4-hydroxycytidine across the blood-placenta barrier. EBioMedicine. 2023; 95:104748. PMC: 10427982. DOI: 10.1016/j.ebiom.2023.104748. View

19.

Malden D, Hong V, Lewin B, Ackerson B, Lipsitch M, Lewnard J . Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment - California, December 2021-May 2022. MMWR Morb Mortal Wkly Rep. 2022; 71(25):830-833. DOI: 10.15585/mmwr.mm7125e2. View

20.

Horby P, Lim W, Emberson J, Mafham M, Bell J, Linsell L . Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 384(8):693-704. PMC: 7383595. DOI: 10.1056/NEJMoa2021436. View