Phenolic compounds of Zanthoxylum armatum DC as potential inhibitors of urease and SARS-CoV2 using molecular docking approach and with simulation study.

The anti-urease effects of active extract and three isolated phenolic compounds viz., chlorogenic acid, trans-ferulic acid, and gallic acid of leaves of Zanthoxylum armatum DC were evaluated. The compounds were identified based on HPLC-PDA, HR-MS, and NMR analysis. Molecular docking analysis revealed that these compounds significantly interacted with Helicobacter pylori urease and SARS-CoV2 vital proteins. Chlorogenic acid was found to show the strongest interaction with the H. pylori urease and coronavirus main protease (Mpro, also called 3CLpro), while gallic acid with five spike proteins (Cathepsin L) of SARS-CoV2. The compounds were checked for their drug-likeliness character and were found to pass the Lipinski filter and abide by Veber's rule and passed through ADMET. Chlorogenic acid was simulated for 50 ns using GROMACS. The study shows that chlorogenic acid isolated from Z. armatum could be a significant antagonist of the H. pylori urease.

Virtual High Throughput Screening to find Suitable Inhibitors for SARSCoV- 2 Main Protease

Background: COVID-19 caused by SARS-CoV-2 virus which originated in Wuhan and quickly spread across various countries has taken the form of a pandemic. It is now a major health concern worldwide and finding a solution to this problem is of utmost importance. Understanding its origin, transmission, and interaction with different compounds is essential to find probable inhibitors. Objective: The objective of our study was to search for potential inhibitors of the main protease of SARS-CoV-2 and to assess their drug-like properties. Methods: In our study, 1909 ligands were filtered through the Lipinski filter and their ADMET properties along with mutagenic nature were analyzed. They were screened for inhibitory activity against the Main Protease of SARS-CoV-2 using BIOVIA Discovery studio. Results: After virtual high throughput screening, two compounds- apigenin and N-(4-bromophenyl)- 7-hydroxy-2-iminochromene-3-carboxamide were found to have promising binding energies as well as –CDOCKER energy scores compared to the reported inhibitor. Conclusion: Apigenin seems to be a potential candidate against the main protease of SARS-CoV-2 and must be considered for further experiments.

Identification of potential plant-based inhibitor against viral proteases of SARS-CoV-2 through molecular docking, MM-PBSA binding energy calculations and molecular dynamics simulation.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, SARS-CoV-2, has recently emerged as a pandemic. Here, an attempt has been made through in-silico high throughput screening to explore the antiviral compounds from traditionally used plants for antiviral treatments in India namely, Tea, Neem and Turmeric, as potential inhibitors of two widely studied viral proteases, main protease (Mpro) and papain-like protease (PLpro) of the SARS-CoV-2. Molecular docking study using BIOVIA Discovery Studio 2018 revealed, (-)-epicatechin-3-O-gallate (ECG), a tea polyphenol has a binding affinity toward both the selected receptors, with the lowest CDocker energy - 46.22 kcal mol-1 for SARS-CoV-2 Mpro and CDocker energy - 44.72 kcal mol-1 for SARS-CoV-2 PLpro, respectively. The SARS-CoV-2 Mpro complexed with (-)-epicatechin-3-O-gallate, which had shown the best binding affinity was subjected to molecular dynamics simulations to validate its binding affinity, during which, the root-mean-square-deviation values of SARS-CoV-2 Mpro-Co-crystal ligand (N3) and SARS-CoV-2 Mpro- (-)-epicatechin-3-O-gallate systems were found to be more stable than SARS-CoV-2 Mpro system. Further, (-)-epicatechin-3-O-gallate was subjected to QSAR analysis which predicted IC50 of 0.3281 nM against SARS-CoV-2 Mpro. Overall, (-)-epicatechin-3-O-gallate showed a potential binding affinity with SARS-CoV-2 Mpro and could be proposed as a potential natural compound for COVID-19 treatment.