Uma Sankar GORLA, Koteswara Rao GSN, Umasankar KULANDAIVELU, Rajasekhar Reddy ALAVALA, Subham DAS, Alex JOSEPH

Bioflavonoids as potential target inhibitors in COVID-19: An in silico analysis

COVID-19, a respiratory pandemic associated with morbidity and mortality due to the lack of FDA approved drugs for the appropriate preventive or treatment strategies. Repurposed drugs such as antiviral and antimalarials are in clinical trials for the development of novel therapeutic agents for the treatment of SARS-CoV-2 infection. The main protease (Mpro) digests replicase polyprotein to generate non-structural proteins and an endoribonuclease (NendoU), a non-structural protein acts as possible targets because of their prominent role in the replication of SARS-CoV-2. In the current study, the bioflavonoids that passed the Lipinski rule were subjected to in silico molecular docking on SARS-CoV-2 main protease and endoribonuclease using Molegro Virtual Docker v6.0. Molecular dynamic simulation studies (20 ns) were carried out to study protein-ligand complex stability by using Schrodinger, LLC’s Maestro Molecular Platform (version 11.8). ADMET properties, target and antiviral potentials were predicted for the top interacting bioflavonoids and significant data were reported. The parameters such as MolDock scores, ReRank scores and interaction poses were predicted for the top interacting phytocompound. In silico analysis showed that hesperetin and malvidin bind effectively at the active site of Mpro and NendoU with a MolDock score of - 100.78 and -86.51 respectively. Molecular dynamic simulations have shown that the protein-ligand complex was stable and exhibits good binding interactions with various amino acids. MM-GBSA studies showed -52.51±5.01 and - 22.80±3.04 free binding energies for hesperetin and malvidin respectively. The current research created a new perspective in understanding hesperetin and malvidin as potent Mpro and NendoU inhibitors, and further research may confirm their therapeutic potentials in COVID-19.

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