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Current Computer-Aided Drug Design

Author(s): Adithya Jayaprakashkamath, Maneesha Murali, Bhagyalakshmi Nair, Feby Benny, Rajalakshmi P. Mani, Darsana Suresh, Aneesh T. Presanna, Amrutha N. Areekkara and Lekshmi R. Nath*

DOI: 10.2174/1573409919666230112123213

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Identification of Kaempferol as Viral Entry Inhibitor and DL-Arginine as Viral Replication Inhibitor from Selected Plants of Indian Traditional Medicine against COVID-19: An in silico Guided in vitro Approach

Page: [313 - 323] Pages: 11

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Abstract

Background: Indian traditional medicinal plants are known for their great potential in combating viral diseases. Previously, we reported a systematic review approach of seven plausible traditional Indian medicinal plants against SARS-CoV-2.

Methods: Molecular docking was conducted with Biovia Discovery Studio. Three binding domains for spike glycoprotein (PDB IDs: 6LZG, 6M17, 6M0J) and one binding domain of RdRp (PDB ID: 7BTF) were used. Among 100 phytoconstituents listed from seven plants by the IMPPAT database used for virtual screening, the best six compounds were again filtered using Swiss ADME prediction and Lipinski's rule. Additionally, a pseudovirion assay was performed to study the interaction of SARS-CoV-2 S1-protein with the ACE 2 receptor to further confirm the effect.

Results: Chebulagic acid (52.06 Kcal/mol) and kaempferol (48.84 Kcal/mol) showed increased interaction energy compared to umifenovir (33.68 Kcal/mol) for the 6LZG binding domain of spike glycoprotein. Epicatechin gallate (36.95 Kcal/mol) and arachidic acid (26.09 Kcal/mol) showed equally comparable interaction energy compared to umifenovir (38.20 Kcal/mol) for the 6M17 binding domain of spike glycoprotein. Trihydroxychalcone (35.23 Kcal/mol) and kaempferol (36.96 Kcal/mol) showed equally comparable interaction energy with umifenovir (36.60 Kcal/mol) for 6M0J binding domain of spike glycoprotein. Upon analyzing the phytoconstituents against RdRp binding domain, DL-arginine (41.78 Kcal/mol) showed comparable results with the positive control remdesivir (47.61 Kcal/mol). ADME analysis performed using Swiss ADME revealed that kaempferol and DL arginine showed drug-like properties with appropriate pharmacokinetic parameters. Further in vitro analysis of kaempferol by pseudovirion assay confirmed an acceptable decrease of the lentiviral particles in transfected HEK293T-hACE2 cells.

Conclusion: The study highlights that kaempferol and DL-arginine could be the significant molecules to exhibit potent action against SARS-CoV-2 and its variants.

Graphical Abstract

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