Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp

Abstract

Background: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality rate and infecting people worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. Objective: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and perform the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties of potential compounds. Methods: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. Results: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/ mol. Among these, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-D-galactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. Conclusion: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

Exploration of CviR-mediated quorum sensing inhibitors from Cladosporium spp. against Chromobacterium violaceum through computational studies

“…Additionally, the pharmacokinetic properties of prospective substances are significantly influenced by the prediction of their physicochemical descriptors 18 . The predicted pharmacokinetic properties of substances such as ADMET are essential for developing innovative drugs with desirable biological activity.…”

“…The open access in silico tools for early prediction of pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of drugs has revolutionized the strategies for disease management. The target ligand molecules' physicochemical parameters and ADMET properties were predicted using the pkCSM ADMET descriptors algorithm, making it easier to find potential treatment possibilities 12 , 18 .…”

Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach

“…Besides, the oral bioavailability of the drug is also a crucial and critical factor in drug design. A higher score lowers the amount of drug that must be delivered to achieve its anticipated pharmacological effect and vice-versa, thereby lowering the risk of side effects and toxicity [ 16 , 17 ]. The higher absorption of the molecules’ gastrointestinal tract naturally leads to improved bioavailability.…”

“…are fungi with the extraordinary ability to produce abundant secondary metabolites with great therapeutic potential [14]. It has been well documented that in silico evaluation of the secondary metabolites through molecular docking, molecular dynamic (MD) simulation and pharmacokinetic properties will have a substantial role in the detection of new metabolites of importance [15][16][17]. Based on the above facts, the main focus of the present study was to identify the new potential compounds from Trichoderma spp.…”

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

“…The bioactive compounds with anti-HIV properties from plant sources may facilitate identifying compounds with inhibitory potential against SARS-CoV-2. In our previous studies, the selected anti-HIV bioactive compounds were evaluated against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and the results of the molecular docking and ADME and Toxicity studies proved to be effective against SARS-CoV-2 [ 24 ]. Hence, a systematic study on in silico-based drug repurposing methods using molecular docking and molecular simulation studies was performed against M pro of SARS-CoV-2 by utilizing the available anti-HIV bioactive compounds from plantsbased on the literature [ 25 , 26 ].Therefore, the present study will help to identify other potential drugs against SARS-CoV-2 [ 25 , 26 , 27 , 28 , 29 , 30 ].…”