High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Olujide O OlubiyiBirgit Strodel

Abstract

We use state-of-the-art computer-aided drug design (CADD) techniques to identify prospective inhibitors of the main protease enzyme, 3CLpro of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. From our screening of over one million compounds including approved drugs, investigational drugs, natural products, and organic compounds, and a rescreening protocol incorporating enzyme dynamics via ensemble docking, we have been able to identify a range of prospective 3CLpro inhibitors. Importantly, some of the identified compounds had previously been reported to exhibit inhibitory activities against the 3CLpro enzyme of the closely related SARS-CoV virus. The top-ranking compounds are characterized by the presence of multiple bi- and monocyclic rings, many of them being heterocycles and aromatic, which are flexibly linked allowing the ligands to adapt to the geometry of the 3CLpro substrate site and involve a high amount of functional groups enabling hydrogen bond formation with surrounding amino acid residues, including the catalytic dyad residues H41 and C145. Among the top binding compounds we identified several tyrosine kinase inhibitors, which include a bioflavonoid, the group of natural products t...Continue Reading

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Citations

Aug 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·R P Vivek-AnanthAreejit Samal
Nov 5, 2020·Briefings in Bioinformatics·Serena DotoloRoberto Tagliaferri
Jan 7, 2021·Briefings in Bioinformatics·Shiv BharadwajVivek Dhar Dwivedi
Feb 10, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Candida ManelfiAlessandro Pedretti
Apr 7, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Gaurav JoshiRamarao Poduri
Apr 18, 2021·Journal of Molecular Modeling·Debarati PaulShubhra Ghosh Dastidar
Jul 31, 2021·Scientific Reports·Gabriel Jiménez-AvalosUNKNOWN COVID-19 Working Group in Perú
Jul 2, 2021·Journal of Chemical Information and Modeling·Ariane Nunes-AlvesRebecca C Wade
Nov 6, 2021·ACS Synthetic Biology·Nícia Rosário-FerreiraIrina S Moreira

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Methods Mentioned

BETA
X-ray
dissection
FRET

Software Mentioned

AutoDock Vina
Gromacs
PyMol
AutoDock Tool
DataWarrior
LigPlot +

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