Chemically modified antiviral peptides against SARS‐CoV‐2

Abstract

To date, the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) COVID‐19 pandemic continues to be a potentially lethal disease. Although both vaccines and specific antiviral drugs have been approved, the search for more specific therapeutic approaches is still ongoing. The infection mechanism of SARS‐CoV‐2 consists of several stages, and each one can be selectively blocked to disrupt viral infection. Peptides are a promising class of antiviral compounds, which may be suitably modified to be more stable, more effective, and more selective towards a specific viral replication step. The latter two goals might be obtained by increasing the specificity and/or the affinity of the interaction with a specific target and often imply the stabilization of the secondary structure of the active peptide. This review is focused on modified antiviral peptides against SARS‐CoV‐2 acting at different stages of virus replication, including ACE2‐RBD interaction, membrane fusion mechanism, and the proteolytic cleavage by different viral proteases. Therefore, the landscape presented herein provides a useful springboard for the design of new and powerful antiviral therapeutics.