An update on emerging therapeutics to combat COVID-19

Basic Clin Pharmacol Toxicol. 2021 Aug;129(2):104-129. doi: 10.1111/bcpt.13600. Epub 2021 Jun 11.

Abstract

Background: The COVID-19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID-19; the clinician needs objective evidence-based medication to treat COVID-19.

Observations: Single-stranded RNA viral genome of SARS-CoV-2 encodes structural proteins (spike protein), non-structural enzymatic proteins (RNA-dependent RNA polymerase, helicase, papain-like protease, 3-chymotrypsin-like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate-limiting steps in viral replications and, therefore, an attractive target for drug development against SARS-CoV-2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID-19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin-converting enzyme (ACE-2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence-based therapeutic regimen exists for COVID-19.

Conclusion: The COVID-19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well-controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.

Keywords: COVID-19; coronavirus; drug repurposing; in vitro; in vivo and in silico.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • COVID-19 / epidemiology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Computer Simulation
  • Drug Repositioning*
  • Humans
  • Pandemics
  • SARS-CoV-2 / drug effects

Substances

  • Antiviral Agents