Ayurvedic Medicinal Plants Against COVID-19: AnIn SilicoAnalysis

Abstract

Even after one and a half years since the outbreak of COVID-19, its complete and effective control is still far from being achieved despite vaccination drives, symptomatic management with available drugs, and wider lockdowns. This has inspired researchers to screen potential phytochemicals from medicinal plants against SARS-CoV-2, adopting a bio-informatics approach. The current study aimed to assess anti-viral activity of the phytochemicals derived from Ayurvedic medicinal plants against SARS-CoV-2 drug targets [3-chymotrypsin-like protease (3CLpro) and RNA dependent RNA polymerase (RdRp)] using validated in silico methods.3D Structures of 196 phytochemicals from three Ayurvedic plants were retrieved from PubChem and KNApSAcK databases and screened for Absorption Distribution Metabolism Excretion and Toxicity(ADMET) to predict drug-likeness. The phytochemicals were subjected to molecular docking and only three showed promise: Acetovanillonewith a binding affinity of −4.7Kcal/mol with RdRp and −4.1 Kcal/mol with 3CL pro; myrtenol with equivalent values of −4.3 Kcal/mol with RdRP and −3.2 Kcal/mol with 3CLpro; and nimbochalcin with equivalent values of −5.0Kcal/mol with RdRp and −4.9 Kcal/mol with 3CLpro. Molecular dynamics simulation (50ns) analysis was made of 3CLpro and RdRp using Autodock Vina 1.1.2 software and VMD software. After ADMET analysis, 78 phytochemicals were found suitable for molecular docking. Three, namely acetovanillone, myrtenol and nimbochalcin from Picrorhiza kurroa, Azadirachta indica and Cyperus rotundus,respectively,exhibited good binding affinity with 3CLproand RdRp of SARS-CoV-2. Interaction analysis, molecular dynamics simulations and MM-PBSA calculations were executed for two complexes, acetovanillone_RdRp and myrtenol_3CL pro.Acetovanillone_RdRpcomplex did not display any structural change after MD simulation as compared to myrtenol_3CL pro. The overall stability of acetovanillone_6NUR was 154.7 kJ/mol, and for myrtenol_1UJ1 90.5 kJ/mol. In silico analysis revealed that acetovanillone ( Picrorhiza kurroa) and myrtenol ( Cyperus rotundus) possess anti SARS-CoV-2 activity. Further studies are needed to validate their efficacy in biological models.

The Mechanism of Chaiyin Particles in the Treatment of COVID-19 Based on Network Pharmacology and Experimental Verification

“…65,66 In addition, many studies have investigated whether traditional medicinal plant extracts exhibit anti-SARS-CoV-2 activity. 67-70…”

Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation Studies of the Molecular Targets and Mechanisms of ChuanKeZhi in the Treatment of COVID-19

“…19 Bharat Krushna Khuntia et al focused on Picrorhizakurroa (Kutki), Azadirachta indica (Neem) and Cyperusrotundus (Mustak), which are widely used in Ayurveda, and performed in silico analysis to reveal the treatment effect in COVID-19. 20 Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules, which belong to TCM, also showed great advantages in improving the clinical symptoms and prognosis of COVID-19 patients in a randomized controlled trial. 21 Currently, TCM combined with western medicine is applied in more than 90% of COVID-19 patients in China and has shown obvious and effective results.…”

Multitargeted Molecular Dynamic Understanding of Butoxypheser Against SARS-CoV-2: An in Silico Study

“…6,7 Most of the previous studies were from single target and multiple drug backgrounds. 18,19 Nevertheless, in this study, we are reporting N-{2-[(2S)-2-Amino-3-methylbutoxy]-6-pro-pylbenzoyl}-L-phenylalanyl-L-serine (Butoxypheser) 20 as the multitargeted inhibitor that has been identified after comprehensive pipeline-based research. We have performed multilevel screening to reduce the computational costs, ie, High-Throughput Virtual Screening (HTVS), Standard Precision (SP), Extra Precise (XP), and Molecular Mechanics/ Generalized Born Surface Area (MMGBSA).…”