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Molecular interactions and inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative.

ABSTRACT: We report molecular interactions and inhibition of the main protease (M^Pro ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of M^Pro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of M^Pro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC₅₀ value of 1.39 ± 0.22 μM, which is comparable to other known inhibitors of this enzyme.

SUBMITTER: Andrzejczyk J

PROVIDER: S-EPMC9347825 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Molecular interactions and inhibition of the SARS-CoV-2 main protease by a thiadiazolidinone derivative.

Andrzejczyk Jacob J Jovic Katarina K Brown Logan M LM Pascetta Valerie G VG Varga Krisztina K Vashisth Harish H

Proteins 20220603 11

We report molecular interactions and inhibition of the main protease (MPro ) of SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the conformational dynamics of MPro via docking protocols and molecular dynamics simulations in all-atom detail. We reveal the local and global dynamics of MPro in the presence of this inhibitor and confirm the inhibition of the enzyme with an IC<su ...[more]

PMID: 35567429

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