Non-structural proteins 2 (nsP2) in Alphavirus: a useful target for drug discovery studies

The Alphavirus genus consists of single-stranded positive-sense ribonucleic acid (RNA) viruses belonging to the Togaviridae family. They are considered arthropod-borne viruses (arboviruses) and the medically most important are: Chikungunya virus (CHIKV), Sindbis virus (SINV), and the three American equine encephalitis viruses, i.e., the Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), and Venezuelan equine encephalitis virus (VEEV). There is currently no approved direct-acting antiviral for the treatment of these diseases. As part of our antiviral drug discovery program focused on Alphaviruses and the non-structural protein 2 (nsP2). We employed diverse in silico methods, ranging from static scanning to temporal pocket evaluation, to assess the druggability of the alphaviral nsP2. Our results suggested that cryptic sites could be better explored for drug discovery campaigns, as current efforts have focused only on the nsP2 active site.