Computer-aided drug design in seeking viral capsid modulators.

Approved or licensed antiviral drugs have limited applications because of their drug resistance and severe adverse effects. By contrast, by stabilizing or destroying the viral capsid, compounds known as capsid modulators prevent viral replication by acting on new targets and, therefore, overcoming the problem of clinical drug resistance. For example, computer-aided drug design (CADD) methods, using strategies based on structures of biological targets (structure-based drug design; SBDD), such as docking, molecular dynamics (MD) simulations, and virtual screening (VS), have provided opportunities for fast and effective development of viral capsid modulators. In this review, we summarize the application of CADD in the discovery, optimization, and mechanism prediction of capsid-targeting small molecules, providing new insights into antiviral drug discovery modalities.