[Antiviral Drugs : Potent Agents, Promising Therapies for COVID‑19 and Therapeutic Limitations]

Overview

Journal Internist (Berl)

Specialty General Medicine

Date 2022 Jan 6

PMID 34988607

Authors

Jakob J Malin

Till Bunse

Christoph D Spinner

Ulrike Protzer

Affiliations

Soon will be listed here.

Abstract

Antiviral drugs inhibit viral replication by interaction with specific elements of the viral replication cycle. Directly acting antiviral agents have revolutionized the therapeutic options for chronic infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). Pharmacological developments constantly improve therapeutic and prophylactic options for diseases caused by herpes viruses, which is of particular relevance for immunocompromised patients. While infections with persistent viruses, such as HIV, HBV or herpes viruses principally so far cannot be cured, complete elimination of viruses that cause acute infections is possible; however, acute infections, such as influenza or coronavirus disease 2019 (COVID-19) offer only a small therapeutic window for antiviral strategies due to their pathophysiological dynamics. The optimal time point for antiviral agents is immediately after exposure to the virus, which frequently limits its application in practice. An effective pre-exposure or postexposure prophylaxis has been established for infections with HIV and influenza A/B and also gains relevance for infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

References

Asselah T, Kowdley K, Zadeikis N, Wang S, Hassanein T, Horsmans Y . Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis. Clin Gastroenterol Hepatol. 2017; 16(3):417-426. DOI: 10.1016/j.cgh.2017.09.027. View

Fielding J, Kelly H, Mercer G, Glass K . Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age. Influenza Other Respir Viruses. 2013; 8(2):142-50. PMC: 4186461. DOI: 10.1111/irv.12216. View

Yoshii N, Tochino Y, Fujioka M, Sakazaki H, Maruyama N, Asai K . The Comparison of the Efficacy of Baloxavir and Neuraminidase Inhibitors for Patients with Influenza A in Clinical Practice. Intern Med. 2020; 59(12):1509-1513. PMC: 7364256. DOI: 10.2169/internalmedicine.4117-19. View

Brockmeyer N . [German-Austrian guidelines for antiretroviral therapy of HIV infection. (July, 2002, update)]. Dtsch Med Wochenschr. 2003; 128 Suppl 1:S7-18. DOI: 10.1055/s-2003-39115. View

Jayk Bernal A, Gomes da Silva M, Musungaie D, Kovalchuk E, Gonzalez A, Delos Reyes V . Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2021; 386(6):509-520. PMC: 8693688. DOI: 10.1056/NEJMoa2116044. View

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y . Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020; 395(10236):1569-1578. PMC: 7190303. DOI: 10.1016/S0140-6736(20)31022-9. View

Zuckerman E, Gutierrez J, Dylla D, de Ledinghen V, Muir A, Gschwantler M . Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection. Clin Gastroenterol Hepatol. 2020; 18(11):2544-2553.e6. DOI: 10.1016/j.cgh.2020.06.044. View

Lehmann C, Malin J, Suarez I, Fatkenheuer G . [Modern HIV treatment]. Internist (Berl). 2019; 60(4):411-419. DOI: 10.1007/s00108-019-0564-0. View

Kluge S, Malin J, Fichtner F, Muller O, Skoetz N, Karagiannidis C . Clinical Practice Guideline: Recommendations on the In-hospital Treatment of Patients with COVID-19. Dtsch Arztebl Int. 2021; 118(50):865-871. PMC: 8948341. DOI: 10.3238/arztebl.m2021.0374. View

10.

Dobson J, Whitley R, Pocock S, Monto A . Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015; 385(9979):1729-1737. DOI: 10.1016/S0140-6736(14)62449-1. View

11.

Gehring A, Protzer U . Targeting Innate and Adaptive Immune Responses to Cure Chronic HBV Infection. Gastroenterology. 2018; 156(2):325-337. DOI: 10.1053/j.gastro.2018.10.032. View

12.

Neumann A, Lam N, Dahari H, Gretch D, Wiley T, Layden T . Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998; 282(5386):103-7. DOI: 10.1126/science.282.5386.103. View

13.

Marty F, Ljungman P, Chemaly R, Maertens J, Dadwal S, Duarte R . Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017; 377(25):2433-2444. DOI: 10.1056/NEJMoa1706640. View

14.

Cohen M, Nirula A, Mulligan M, Novak R, Marovich M, Yen C . Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial. JAMA. 2021; 326(1):46-55. PMC: 8176388. DOI: 10.1001/jama.2021.8828. View

15.

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

16.

Pan H, Peto R, Henao-Restrepo A, Preziosi M, Sathiyamoorthy V, Abdool Karim Q . Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2020; 384(6):497-511. PMC: 7727327. DOI: 10.1056/NEJMoa2023184. View

17.

Gruell H, Vanshylla K, Tober-Lau P, Hillus D, Schommers P, Lehmann C . mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat Med. 2022; 28(3):477-480. PMC: 8767537. DOI: 10.1038/s41591-021-01676-0. View

18.

Spinner C, Gottlieb R, Criner G, Lopez J, Cattelan A, Soriano Viladomiu A . Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324(11):1048-1057. PMC: 7442954. DOI: 10.1001/jama.2020.16349. View

19.

Duwe S, Schmidt B, Gartner B, Timm J, Adams O, Fickenscher H . Prophylaxis and treatment of influenza: options, antiviral susceptibility, and existing recommendations. GMS Infect Dis. 2021; 9:Doc02. PMC: 8165743. DOI: 10.3205/id000071. View

20.

Weinreich D, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R . REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med. 2021; 385(23):e81. PMC: 8522800. DOI: 10.1056/NEJMoa2108163. View