Virtual screening of peptides with high affinity for SARS-CoV-2 main protease

Abstract

The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 2,000,000 deaths worldwide. Currently, vaccine development and drug repurposing have been the main strategies to find a COVID-19 treatment. However, the development of new drugs could be the solution if the main strategies fail. Here, a virtual screening of pentapeptides was applied in order to identify peptides with high affinity to SARS-CoV-2 main protease (Mpro). Over 70,000 peptides were screened employing a genetic algorithm that uses a docking score as the fitness function. The algorithm was coupled with a RESTful API to persist data and avoid redundancy. The docking exhaustiveness was adapted to the number of peptides in each virtual screening step, where the higher the number of peptides, the lower the docking exhaustiveness. Two potential peptides were selected (HHYWH and HYWWT), which have higher affinity to Mpro than to human proteases. Albeit preliminary, the data presented here provide some basis for the rational design of peptide-based drugs to treat COVID-19.