A computational study of the reactivity in the main protease of SARS-CoV-2 to guide the design of inhibitors

A computational study of the reactivity in the main protease of SARS-CoV-2 to guide the design of inhibitors is led by Prof. Iñaki Tuñón from the University of Valencia, Spain. Over two and a half months, the team will analyse the binding of the substrate and the reaction mechanisms of the main protease of SARS-CoV-2 (the virus strain causing disease COVID-19). The main protease (3CLpro) is an enzyme with essential role during the replication of the virus and is therefore an attractive drug target. That is why one of the strategies for the development of potential treatments against the SARS-CoV-2 is based on the disruption of the activity of those enzymes that are vital in the replication cycle of the virus, using adequate compounds. The project led by Prof. Iñaki Tuñón is structured in three work packages and there are five expected outcomes. One of those is the definition of the binding mode of different inhibitors and to propose a chemical modification of the inhibitors to improve their binding to the 3CLpro enzyme. All this supports the overall goal of the team to use the knowledge obtained from the simulation of the catalytic process to guide the design of more potent inhibitors to block the main protease of SARS-CoV-2. These complex studies require high computational power and PRACE awarded the group with 23 000 000 core hours on the main partition of MareNostrum4, hosted by BSC, Spain, as well as 288 000 core hours on its P9/V100 partition.