Publication: In Silico Binding Role of Flavonoids as SARS-CoV-2 Main Protease (Mpro) Inhibitors: A Molecular Docking Simulation-Based Virtual Screening
Date
2023
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
International Medical University
Abstract
Around December 2019, news reports of a mysterious pneumonia-like disease started making
headlines. Later discovered to be a novel SARS-CoV-2 virus, the world was woefully
underprepared for its aggressiveness. Since the World Health Organization declared a global
pandemic in March 2020, the virus has infected and killed millions of individuals worldwide
without discrimination. Due to the lack of SARS-CoV-2-specific treatment options and
rapidly mutating variants, the virus triggered waves of infection and death. Computer-assisted
drug design techniques have allowed rapid virtual screening and molecular docking for the
identification of numerous biological hit compounds. This study used the Schrodinger
software to perform high-throughput virtual screening on a flavonoid derivative database
consisting of 2055 compounds against the SARS-CoV-2 main protease 6LU7. The Glide
Docking scores narrowed the database to ten hit molecules with the PubChem CIDs 1882879,
1866522, 941256, 5703289, 626515, 1974731, 654250, 5490127, 941927, and 5282073.
Their scores ranged between -8.073, -7.981, -7.754, -7.933, -7.911, -7.903, -7.875, -7.854, -
7.826, and -7.821 kcal/mol, respectively. They were also studied for their binding properties,
including binding interactions, binding orientation and binding energies. The compounds had
hydrogen bonds ranging from 1 to 3, and the hydrogen bond interacting residues were HID
164, LEU 141, GLU 166, SER 144, HID 163, and GLY 143. Significantly inhibiting the
main protease activity of SARS-CoV-2 are ligands that are capable of creating hydrogen
bond interactions with these amino acids, which are considered invaluable during viral
replication and transcription. Ergo, these findings suggest that such compounds might indeed
inhibit the SARS-CoV-2 main protease 6LU7. These compounds can be developed into
viable drug candidates following structural optimization, in vitro studies, in vivo studies, and
human clinical trials. Hopefully, other scientists can use the results of this study to develop
lifesaving treatments for those affected by the SARS-CoV-2 virus.
Description
Keywords
In Vitro Techniques, SARS-CoV-2, Coronavirus, Amino Acids