Broad-spectrum prodrugs with anti-SARS-CoV-2 activities: Strategies, benefits, and challenges

J Med Virol. 2022 Apr;94(4):1373-1390. doi: 10.1002/jmv.27517. Epub 2021 Dec 18.

Abstract

In this era, broad-spectrum prodrugs with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activities are gaining considerable attention owing to their potential clinical benefits and role in combating the fast-spreading coronavirus disease 2019 (COVID-19) pandemic. The last 2 years have seen a surge of reports on various broad-spectrum prodrugs against SARS-CoV-2, and in in vitro studies, animal models, and clinical practice. Currently, only remdesivir (with many controversies and limitations) has been approved by the U.S. FDA for the treatment of SARS-CoV-2 infection, and additional potent anti-SARS-CoV-2 drugs are urgently required to enrich the defense arsenals. The world has ubiquitously grappled with the COVID-19 pandemic, and the availability of broad-spectrum prodrugs provides great hope for us to subdue this global threat. This article reviews promising treatment strategies, antiviral mechanisms, potential benefits, and daunting clinical challenges of anti-SARS-CoV-2 agents to provide some important guidance for future clinical treatment.

Keywords: COVID-19; SARS-CoV-2; benefits; broad-spectrum; challenges; prodrugs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Anti-Infective Agents / therapeutic use
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment
  • Humans
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Prodrugs / therapeutic use
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Viral Proteins / antagonists & inhibitors

Substances

  • Anti-Infective Agents
  • Antiviral Agents
  • Prodrugs
  • Viral Proteins