Molecular docking, Molecular dynamics, and AD-MET investigation of selected phytochemicals as promising inhibitors of SARS-CoV-19 targets

There are a few small organic molecules against SARS-CoV-2 that has been discovered since the epidemic commenced in November 2019. The con-ventional medication discovery approach demands more than a decade of the year of laborious research and development and substantial financial commitment, which is not achievable in the face of the current epidemic. This study aims to discover and recognize the most effective and promising molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 120 phytochemicals from six different Ayurveda medicinal plants. The binding affinities were studied using a structure-based drug design of molecular docking, divulging 10 molecules possessing greater affinity towards the target than the reference drug molnupiravir. Molecular docking analysis identified 10 phytochemicals, castalagin, wedelolactone, arjungenin, bet-ulin, galbacin, shinpterocarpin, liquiritin, cordioside, licopyranocoumarin, and daucosterol from different kinds of ayurvedic medicinal plants phyto-chemicals possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely castalagin and wedelolactone, with low binding energies, were the most promising. Furthermore, we carried out MD simulations for the castalagin-protein complexes based on the docking score. Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike the protein of SARS-CoV-2. © 2023, Zita Medical Managent. All rights reserved.

An in silico investigation to identify promising inhibitors for SARS-CoV-2 Mpro target.

BACKGROUND: 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 Ayurveda medicinal plants. METHODS: The phytochemicals were downloaded from 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 (-7.0 kcal/mol) against SARS-CoV-2-Mpro. CONCLUSION: Two molecules, namely sennoside-B, and isotrilobine with low binding energies, were the 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.

Drug Repurposing: An Effective Tool in Modern Drug Discovery.

Drug repurposing is using an existing drug for a new treatment that was not indicated before. It has received immense attention during the COVID-19 pandemic emergency. Drug repurposing has become the need of time to fasten the drug discovery process and find quicker solutions to the over-exerted healthcare scenario and drug needs. Drug repurposing involves identifying the drug, evaluating its efficiency using preclinical models, and proceeding to phase II clinical trials. Identification of the drug candidate can be made through computational and experimental approaches. This approach usually utilizes public databases for drugs. Data from primary and translational research, clinical trials, anecdotal reports regarding off-label uses, and other published human data information available are included. Using artificial intelligence algorithms and other bioinformatics tools, investigators systematically try to identify the interaction between drugs and protein targets. It can be combined with genetic data, clinical analysis, structure (molecular docking), pathways, signatures, targets, phenotypes, binding assays, and artificial intelligence to get an optimum outcome in repurposing. This article describes the strategies involved in drug repurposing and enlists a series of repurposed drugs and their indications.

Computational search for potential COVID-19 drugs from ayurvedic medicinal plants to identify potential inhibitors against SARS-CoV-2 targets.

BACKGROUND: To date, very few small drug molecules are used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been discovered since the epidemic commenced in November 2019. SARS-CoV-2 RdRp and spike protein are essential targets for drug development amidst whole variants of coronaviruses. OBJECTIVE: This study aims to discover and recognize the most effective and promising small molecules against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and spike protein targets through molecular docking screening of 39 phytochemicals from five different Ayurveda medicinal plants. METHODS: The phytochemicals were downloaded from PubChem, and SARS-CoV-2 RdRp and spike protein were taken from the protein data bank. The molecular interactions, binding energy, and ADMET properties were analyzed. RESULTS: Molecular docking analysis identified some phytochemicals, oleanolic acid, friedelin, serratagenic acid, uncinatone, clemaphnol A, sennosides B, trilobine and isotrilobine from ayurvedic medicinal plants possessing greater affinity against SARS-CoV-2-RdRp and spike protein targets. Two molecules, namely oleanolic acid and sennosides B, with low binding energies, were the most promising. Furthermore, based on the docking score, we carried out MD simulations for the oleanolic acid and sennosides B-protein complexes. CONCLUSION: Molecular ADMET profile estimation showed that the docked phytochemicals were safe. The present study suggested that active phytochemicals from medicinal plants could inhibit RdRp and spike protein of SARS-CoV-2.

IDENTIFICATION OF PROMISING PHYTOCHEMICAL INHIBITORS FOR SARS- CoV-2 FROM ROSA CENTIFOLIA BY INSILICO DOCKING STUDIES

Since November 2019, no cost-effective and potential small drug molecule has been discovered against the SARS-CoV-2 pandemic. The major disadvantage of conventional synthesis is the laborious research time for discovery and development with a huge economy that is not easily met by current pandemic conditions. The main aim of this study is to discover and identify the most effective and promising molecules against the three targets of SARS-CoV-2, such as protease, spike protein and RdRp, via molecular docking screening of various phytochemicals from Rosa Centifolia. The binding affinities were studied using a structure-based drug design of molecular docking. The study results showed that most constituents possess good affinity towards the target than standard drug N3 inhibitor. Among 27 compounds, multiflorin B showed the highest binding energies of -6.975, and -5.471 kcal/mol against protease and RdRp targets, respectively. The compound sabinene showed good interaction with spike protein with a docking score of -4.449 kcal/mol. Molecular ADMET profile estimation showed that the docked phytochemicals are safe. The present study indicates that the various active phytochemical constituents of Rosa Centifolia could inhibit SARS-CoV-2. © 2022 Deuton-X Ltd. All rights reserved.