Although vaccine development is being undertaken at a breakneck speed, there is currently no effective antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19. Therefore, the present study aims to explore the possibilities offered by naturally available and abundant flavonoid compounds, as a prospective antiviral drug to combat the virus. A library of 44 citrus flavonoids was screened against the highly conserved Main Protease (M pro) of SARS-CoV-2 using molecular docking. The compounds which showed better CDocker energy than the co-crystal inhibitor of M pro were further revalidated by flexible docking within the active site; followed by assessment of drug likeness and toxicity parameters. The non-toxic compounds were further subjected to molecular dynamics simulation and predicted activity (IC 50) using 3D-QSAR analysis. Subsequently, hydrogen bonds and dehydration analysis of the best compound were performed to assess the binding affinity to M pro. It was observed that out of the 44 citrus flavonoids, five compounds showed lower binding energy with M pro than the co-crystal ligand. Moreover, these compounds also formed H-bonds with two important catalytic residues His41 and Cys145 of the active sites of M pro. Three compounds which passed the drug likeness filter showed stable conformation during MD simulations. Among these, the lowest predicted IC 50 value was observed for Taxifolin. Therefore, this study suggests that Taxifolin, could be a potential inhibitor against SARS-CoV-2 main protease and can be further analysed by in vitro and in vivo experiments for management of the ongoing pandemic.

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Background: Entamoeba histolytica is the primary protozoa which causes amoebic dysentery and is prioritized as the third most prevalent parasitosis. Drug of choice in amoebic dysentery is metronidazole but it has unpleasant side effects with reports of development of resistance in certain cases. Homalomena aromatica Schott. is a plant which is used in different ethnomedicinal practices of south-east Asia to treat stomach ailments and against intestinal parasites. Objective: In the present study, a docking weighted network pharmacology based approach was employed to understand the effects of a library of 71 natural molecules reported from Homalomena aromatica with reference to four proteins of Entamoeba histolytica namely thioredoxin reductase, cysteine synthase, glyceraldehyde-3-phosphate dehydrogenase, ornithine decarboxylase. Method: Molecular docking of the phytoconstituents of H. aromatica was performed in Biovia Discovery Studio 2017 R2 software suit on the selected proteins of E. histolytica. A connection was established between the proteins and molecules via network pharmacology weighted docking studies with the help of Cytoscape V3.4.0 software. Quantum mechanics based Density Functional Theory (DFT) analysis was performed to ascertain the viability of the filtered molecules. Results: On basis of the docking studies of the natural molecules on the selected protein targets, a network of molecules was build. DFT based minimum energy gap was analysed to further ascertain the most potential inhbitors. Three molecules from H. aromatica; 3,7-dimethylocta-1,6-dien-3-yl acetate, α-methyl-α-(4-methyl-3-pentenyl)-oriranemethanol, 7-octadiene-2,6-diol-2,6-dimethyl were predicted to be potential lead molecules against amoebiasis. Conclusion: The present study would provide important evidence in development of new drug molecules to treat amoebiasis.

Background: Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of north east India. Objective: In this study, the anti malarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification via in silico study. Method: On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta. Results: The IC50 of the methanol extract of Coptis teeta 0.08 µg/ml in 3D7 strain and 0.7 µg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the band gap energy of noroxyhydrastinine was found to be 0.186 Ha indicating a favourable interaction. Conclusion: The in silico analysis as an addition to the in vitro results provide strong evidence of noroxyhydrastinine as an anti malarial agent.

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