Phylogenetic network analysis of SARS-CoV-2 Mpro protease and the in silico screening of bioactive compounds from Philippine medicinal plants as potential Mpro inhibitors

• Main Author: Villanueva, Jose Antonio B.
• Format: text
• Language: English
• Published: Animo Repository 2021
• Subjects: COVID-19 (Disease); Phytochemicals; Medicinal plants > Philippines; Bioactive compounds; Phylogeny; Biology
• Online Access: https://animorepository.dlsu.edu.ph/etdb_bio/1
• Institution: De La Salle University

The novel coronavirus strain, Severe Acute Respiratory Syndrome- Coronavirus‐2 (SARS‐CoV‐2), is currently spreading globally in a pandemic. There is presently no specific antiviral therapeutic agent against SARS-CoV-2 while vaccination is currently rolled out worldwide. Scientists resort to drug repurposing in the hope that pharmaceutically-approved antivirals and natural phytochemical compounds might work against the virus. Numerous phytochemicals were reported to limit the spread of SARS-CoV-2 by inhibiting the main protease (Mpro) which is essential for viral replication. In this study, an in silico approach was used to determine the potential of biologically active phytocompounds from 16 Philippine medicinal plants in potentially blocking the Mpro of SARS-CoV-2. Initially, available gene sequences of Mpro were collected from Global Initiative on Sharing All Influenza Data (GISAID) and analyzed by multiple alignment and phylogenetic rendering to determine evolutionary relationships and identify a candidate representative for subsequent docking. Analysis showed that Mpro sequences of the variants were 100% similar which suggests a high degree of conservation. Autodock Vina binding energy docking scores of the top two best phytocompound ligands, amentoflavone (−9.4 kcal/mol) from Cycas revoluta and gallocatechin gallate (−8.7 kcal/mol) from Schizolobium parahyba, showed promising results when compared to the reference drug inhibitor lopinavir (−8.5 kcal/mol). Pharmacophore modeling via Pharmagist generated a general overview of the structural parts of the ligand that can predictably interact with the Mpro active site residues. CABS-flex molecular dynamics simulation verified the stability of the ligand-Mpro complex, with the root-mean-square fluctuation (RMSF) results of which revealed stable amino acid configurations which were not significantly different from the apo-Mpro (p > 0.05). Despite amentoflavone and gallocatechin gallate violating Lipinski’s rules in the assessment of druglikeness, the scoring for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) afforded favorable results and suggest the potential to be candidate inhibitors of SARS-CoV-2.