In:
Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 19, No. 9 ( 2023-11), p. 925-938
Abstract:
A limited number of small molecules against SARS-CoV-2 has been discovered since
the epidemic commenced in November 2019. The conventional medicinal chemistry approach demands more than a decade of the year of laborious research and development and a substantial financial
commitment, which is not achievable in the face of the current epidemic. Objective: This study aims to discover and recognize the most effective and promising small molecules
by interacting SARS-CoV-2 Mpro target through computational screening of 39 phytochemicals from five different Ayurvedic medicinal plants. Methods: The phytochemicals were downloaded from Research Collaboratory for Structural Bioinformatics
(RCSB) Protein Data Bank (PDB) PubChem, and the SARS-CoV-2 protein (PDB ID: 6LU7; Mpro) was taken from the PDB. The molecular interactions, binding energy, and ADMET
properties were analyzed. Results: The binding affinities were studied using a structure-based drug design of molecular docking,
divulging 21 molecules possessing greater to equal affinity towards the target than the reference standard. Molecular docking analysis identified 13 phytochemicals, sennoside-B (-9.5 kcal/mol),
isotrilobine (-9.4 kcal/mol), trilobine (-9.0 kcal/mol), serratagenic acid (-8.1 kcal/mol), fistulin (-8.0 kcal/mol), friedelin (-7.9 kcal/mol), oleanolic acid (-7.9 kcal/mol), uncinatone (-7.8 kcal/mol), 3,4-di-
O-caffeoylquinic acid (-7.4 kcal/mol), clemaphenol A (-7.3 kcal/mol), pectolinarigenin (-7.2 kcal/mol), leucocyanidin (-7.2 kcal/mol), and 28-acetyl botulin (-7.2 kcal/mol) from ayurvedic medicinal
plants phytochemicals possess greater affinity than the reference standard Molnupiravir (-7.0 kcal/mol) against SARS-CoV-2-Mpro. Conclusion: Two molecules, namely sennoside-B, and isotrilobine with low binding energies, were
predicted as most promising. Furthermore, we carried out molecular dynamics simulations for the sennoside-B protein complexes based on the docking score. ADMET properties prediction confirmed
that the selected docked phytochemicals were optimal. These compounds can be investigated further and utilized as a parent core molecule to create novel lead molecules for preventing COVID-19.
Type of Medium:
Online Resource
ISSN:
1573-4064
DOI:
10.2174/1573406419666230413112802
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2023
SSG:
15,3
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