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Topological analysis of SARS CoV-2 main protease.

ABSTRACT: There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (M^pro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free M^pro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SARS CoV-2 M^pro is 1900% more sensitive than SARS CoV-1 M^pro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of M^pro to structural perturbations is located exactly around the catalytic site Cys-145 and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 M^pro.

SUBMITTER: Estrada E

PROVIDER: S-EPMC7286701 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Topological analysis of SARS CoV-2 main protease.

Estrada Ernesto E

Chaos (Woodbury, N.Y.) 20200601 6

There is an urgent necessity of effective medication against severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which is producing the COVID-19 pandemic across the world. Its main protease (M<sup>pro</sup>) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free M<sup>pro</sup> shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here, we report that average SA ...[more]

PMID: 32611087

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