Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Phytochemicals*/metabolism ; Phytochemicals*/pharmacology ; Spike Glycoprotein, Coronavirus*/metabolism ; COVID-19 Drug Treatment*; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protein Binding ; SARS-CoV-2 ; Small Molecule Libraries

SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as "coronavirus disease 2019" (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of -14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package.

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Keywords: SARS-CoV-2; drug targets; molecular docking; molecular dynamic simulation; phytochemicals

0 (Antiviral Agents)
0 (Phytochemicals)
0 (Small Molecule Libraries)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)

Date Created: 20220423 Date Completed: 20220426 Latest Revision: 20221207

20240105

PMC9025634

10.3390/molecules27082401

35458599