Jump to main content
Jump to site search

Issue 7, 2021
Previous Article Next Article

Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Author affiliations

Abstract

During the last forty years we have witnessed impressive advances in the field of antiviral drug discovery culminating with the introduction of therapies able to stop human immunodeficiency virus (HIV) replication, or cure hepatitis C virus infections in people suffering from liver disease. However, there are important viral diseases without effective treatments, and the emergence of drug resistance threatens the efficacy of successful therapies used today. In this review, we discuss strategies to discover antiviral compounds specifically designed to combat drug resistance. Currently, efforts in this field are focused on targeted proteins (e.g. multi-target drug design strategies), but also on drug conformation (either improving drug positioning in the binding pocket or introducing conformational constraints), in the introduction or exploitation of new binding sites, or in strengthening interaction forces through the introduction of multiple hydrogen bonds, covalent binding, halogen bonds, additional van der Waals forces or multivalent binding. Among the new developments, proteolysis targeting chimeras (PROTACs) have emerged as a valid approach taking advantage of intracellular mechanisms involving protein degradation by the ubiquitin-proteasome system. Finally, several molecules targeting host factors (e.g. human dihydroorotate dehydrogenase and DEAD-box polypeptide 3) have been identified as broad-spectrum antiviral compounds. Implementation of herein described medicinal chemistry strategies are expected to contribute to the discovery of new drugs effective against current and future threats due to emerging and re-emerging viral pandemics.

Graphical abstract: Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Back to tab navigation

Supplementary files

Article information


Submitted
24 Oct 2020
First published
17 Feb 2021

Chem. Soc. Rev., 2021,50, 4514-4540
Article type
Review Article

Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses

Y. Ma, E. Frutos-Beltrán, D. Kang, C. Pannecouque, E. De Clercq, L. Menéndez-Arias, X. Liu and P. Zhan, Chem. Soc. Rev., 2021, 50, 4514
DOI: 10.1039/D0CS01084G

Social activity

Search articles by author

Spotlight

Advertisements