In silico analysis of Phyllanthus amarus phytochemicals as potent drugs against SARS-CoV-2 main protease

Abstract

Phyllanthus amarus , also known as Bhui Korma in India, is well known for its medicinal properties and is used to treat several diseases worldwide. This study aims to identify phytochemicals from P. amarus and assess their anti-viral activity through in silico methods against the main protease (M Pro ) enzyme of the novel coronavirus. 190 compounds were obtained from literature and docked against 3CLPro and 16 compounds showed great binding affinity with 3CLPro with their values lying between -8.9 kcal/mol to -9.6 kcal/mol. The top two compounds, Myricitrin (CID: 5352000) and Quercetin-3-O-glucuronide (CID: 12004528) gave high binding affinity values of -9.6 kcal/mol and -9.4 kcal/mol respectively and also display favourable binding interactions with the M Pro . Both the compounds were further subjected to molecular dynamics simulation and MM-PBSA based binding free energy calculations. ADMET and drug-likeness properties were studied to assess the pharmacokinetic properties of the compounds. Favourable pharmacokinetic results reinforced the applicability of the compounds assessed. Along with continuous studies being carried out with chemical compounds, research needs to expand into all areas, including the use of natural compounds as drug compounds. The identified hits from this study can be taken further for in vitro and in vivo studies to examine their efficacy against COVID-19.

The interaction capabilities of phytoconstituents of ethanolic seed extract of cumin (Cuminum cyminum L.) with HMG‐CoA reductase to subside the hypercholesterolemia: A mechanistic approach

“…Nevertheless, about the end of simulation, the optimum SASA peaks were observed that indicate that by the end of the simulation more of the ligand is interred into the protein, rather than interacting with the aqueous environment (Martins et al., 2014). Accordingly, the suitable plots of free energy of solvation energy, average angle interaction and distribution indicate the compatibilities with the pocket of active site (Murthy et al., 2021). The cuminaldehyde is a key ingredient of the cumin that was reported to have antimicrobial, antioxidants, anti‐inflammatory and hypolipidemic potential (Morshedi et al., 2015).…”

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach

“…Besides, Indian medicinal plants have been known for their remarkable anti-inflammatory, anti-allergic, anti-bacterial, anti-fungal, immunomodulatory, and anti-viral inhibitory effects against a wide range of pathogenic infections [ 25 ]. Earlier, the extracts and phytochemical compounds of Decalepis hamiltonii, Acacia modesta, Hypericum perforatum, Phylanthus amarus, and Phyllanthus emblica have shown remarkable efficacy against viruses like chikungunya, hepatitis, herpes, and bronchitis [ 26 , 27 , 28 , 29 , 30 ]. Hence, new antiviral strategies must take advantage of the antiviral inhibitory properties of naturally occurring phytochemical compounds instead of focusing only on synthetic substances.…”

Identification of Potential Antiviral Inhibitors from Hydroxychloroquine and 1,2,4,5-Tetraoxanes Analogues and Investigation of the Mechanism of Action in SARS-CoV-2

“…The 3CLpro/MPro activity site is found in the gap between domains I and II, consisting of a Cys-His catalytic dyad (Cys145 and His41) [48]. The active pocket consists of hydrophobic amino acids such as Tyr54, Met49, Met165, Phe140, Leu141, Cys145, Leu27, Pro168, Leu167, Cys145, Ala191, Cys44, Leu50, and Met40, which provide a relatively hydrophobic environment to contain the compound and stabilize its conformation.…”

“…Validation of the molecular docking protocols for the crystal structure of the main protease (Mpro) COVID-19 in complex with 11b inhibitor *. According to Gowtham et al (2008) [44] and Hevener et al (2009)[45], the predicted binding mode using molecular docking indicates that when the RMSD is less than 2.0 Å in relation to the crystallographic pose of a respective ligand, the validation is considered satisfactory[46,47].The 3CLpro/MPro activity site is found in the gap between domains I and II, consisting of a Cys-His catalytic dyad (Cys145 and His41)[48]. The active pocket consists of…”