In silico screening and molecular dynamics of phytochemicals from Indian cuisine against SARS-CoV-2 MPro.

SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 MPro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ≥ -8.0 kcal/mol were selected to understand their interaction with MPro. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 MPro. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of MPro were mediated through the OH, SH, NH2 and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to MPro with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Re-Potentiation of ß-Lactam Antibiotic by Synergistic Combination with Biogenic Copper Oxide Nanocubes against Biofilm Forming Multidrug-Resistant Bacteria.

Biofilm-associated tissue and device infection is a major threat to therapy. The present work aims to potentiate ß-lactam antibiotics with biologically synthesized copper oxide nanoparticles. The synergistic combination of amoxyclav with copper oxide nanoparticles was investigated by checkerboard assay and time-kill assay against bacteria isolated from a burn wound and a urinary catheter. The control of biofilm formation and extracellular polymeric substance production by the synergistic combination was quantified in well plate assay. The effect of copper oxide nanoparticles on the viability of human dermal fibroblasts was evaluated. The minimum inhibitory concentration and minimum bactericidal concentration of amoxyclav were 70 µg/mL and 140 µg/mL, respectively, against Proteus mirabilis and 50 µg/mL and 100 µg/mL, respectively, against Staphylococcus aureus. The synergistic combination of amoxyclav with copper oxide nanoparticles reduced the minimum inhibitory concentration of amoxyclav by 16-fold against P. mirabilis and 32-fold against S. aureus. Above 17.5 µg/mL, amoxyclav exhibited additive activity with copper oxide nanoparticles against P. mirabilis. The time-kill assay showed the efficacy of the synergistic combination on the complete inhibition of P. mirabilis and S. aureus within 20 h and 24 h, respectively, whereas amoxyclav and copper oxide nanoparticles did not inhibit P. mirabilis and S. aureus until 48 h. The synergistic combination of amoxyclav with copper oxide nanoparticles significantly reduced the biofilm formed by P. mirabilis and S. aureus by 85% and 93%, respectively. The concentration of proteins, carbohydrates, and DNA in extracellular polymeric substances of the biofilm was significantly reduced by the synergistic combination of amoxyclav and copper oxide nanoparticles. The fibroblast cells cultured in the presence of copper oxide nanoparticles showed normal morphology with 99.47% viability. No cytopathic effect was observed. Thus, the study demonstrated the re-potentiation of amoxyclav by copper oxide nanoparticles.