Revealing the Molecular Mechanisms of Proteolysis of SARS-CoV-2 Mpro from QM/MM Computational Methods.

13 May 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


SARS-CoV-2 Mpro is one of the enzymes essential for the replication process of the virus responsible of the COVID-19 pandemic. This work is focused on exploring its proteolysis reaction by means of QM/MM methods. The resulting free energy landscape of the process provides valuable information on the species appearing along the reaction path and suggests that the mechanism of action of this enzyme, taking place in four steps, slightly differs from other cysteine proteases. Our predictions, supported by the agreement with some recently published experimental data, can be used to guide the design of COVID-19 antiviral compounds with clinical potential.


SARS-CoV-2 Mpro
Free Energy Landscape
Cysteine protease


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