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Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies.

Authors :
Murali, Mahadevamurthy
Gowtham, Hittanahallikoppal Gajendramurthy
Shilpa, Natarajamurthy
Krishnappa, Hemanth Kumar Naguvanahalli
Ledesma, Ana E.
Jain, Anisha S.
Shati, Ali A.
Alfaifi, Mohammad Y.
Elbehairi, Serag Eldin I.
Achar, Raghu Ram
Silina, Ekaterina
Stupin, Victor
Ortega-Castro, Joaquín
Frau, Juan
Flores-Holguín, Norma
Amruthesh, Kestur Nagaraj
Shivamallu, Chandan
Kollur, Shiva Prasad
Glossman-Mitnik, Daniel
Source :
Molecules. Dec2022, Vol. 27 Issue 23, p8288. 16p.
Publication Year :
2022

Abstract

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than −8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of −10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (−10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study. [ABSTRACT FROM AUTHOR]

Subjects

Subjects :
*SARS-CoV-2
*COVID-19

Details

Language :
English
ISSN :
14203049
Volume :
27
Issue :
23
Database :
Academic Search Index
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
160739808
Full Text :
https://doi.org/10.3390/molecules27238288