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Microbial Natural Products as Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro).


ABSTRACT: The main protease (Mpro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski's rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme's conformers. Final MDS experiments were performed on the ligand-protein complexes (compounds 1-12, Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds (1-6) was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the Mpro structural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2.

SUBMITTER: Sayed AM 

PROVIDER: S-EPMC7409236 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Microbial Natural Products as Potential Inhibitors of SARS-CoV-2 Main Protease (M<sup>pro</sup>).

Sayed Ahmed M AM   Alhadrami Hani A HA   El-Gendy Ahmed O AO   Shamikh Yara I YI   Belbahri Lassaad L   Hassan Hossam M HM   Abdelmohsen Usama Ramadan UR   Rateb Mostafa E ME  

Microorganisms 20200629 7


The main protease (M<sup>pro</sup>) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski's rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good bindin  ...[more]

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