Computational identification of potential lead molecules targeting rho receptor of Neisseria gonorrhoeae.

Gonorrhea, one of the sexually transmitted disease caused by a gram negative diplococcus bacteria Neisseria gonorrhoeae. Rho protein is indispensable for bacterial viability due to its versatile functions in physiology apart from RNA dependent transcription termination. Based on conserved function and wider role in several cellular processes, inhibitors specifically targeting Rho proteins are largely in use these days to treat various bacterial infections. In this study, three dimensional structure of Rho protein was modeled using the template protein from E. coli and further the optimized model was simulated for 100 ns to understand the structural stability and compactness. Owing to the therapeutic potential of Rho, traditional structure-based virtual screening was applied to identify potential inhibitors for the selected target. Based on empirical glide scoring functions two potent lead molecules (ChemBridge_6121956 and ChemBridge_5232688) were selected from ChemBridge database. The pharmacokinetic properties of these lead molecules are within the permissible range. DFT descriptor revealed that the lead molecules are more reactive, which also supports the molecular docking studies. The stability of Rho and Rho-inhibitor complexes was studied using molecular dynamics simulation. Parameters include binding free energy calculation, RMSD, RMSF and hydrogen bond analysis depicts the stability of Rho and Rho-inhibitors throughout the simulation. Altogether, the identified lead molecules require further optimization towards the design and development of new antibiotics against N. gonorrhoeae.Communicated by Ramaswamy H. Sarma.

In silico Screening of Natural Phytocompounds Towards Identification of Potential Lead Compounds to Treat COVID-19.

COVID-19 is one of the members of the coronavirus family that can easily assail humans. As of now, 10 million people are infected and above two million people have died from COVID-19 globally. Over the past year, several researchers have made essential advances in discovering potential drugs. Up to now, no efficient drugs are available on the market. The present study aims to identify the potent phytocompounds from different medicinal plants (Zingiber officinale, Cuminum cyminum, Piper nigrum, Curcuma longa, and Allium sativum). In total, 227 phytocompounds were identified and screened against the proteins S-ACE2 and M pro through structure-based virtual screening approaches. Based on the binding affinity score, 30 active phytocompounds were selected. Amongst, the binding affinity for beta-sitosterol and beta-elemene against S-ACE2 showed -12.0 and -10.9 kcal/mol, respectively. Meanwhile, the binding affinity for beta-sitosterol and beta-chlorogenin against M pro was found to be -9.7 and -8.4 kcal/mol, respectively. Further, the selected compounds proceeded with molecular dynamics simulation, prime MM-GBSA analysis, and ADME/T property checks to understand the stability, interaction, conformational changes, binding free energy, and pharmaceutical relevant parameters. Moreover, the hotspot residues such as Lys31 and Lys353 for S-ACE2 and catalytic dyad His41 and Cys145 for M pro were actively involved in the inhibition of viral entry. From the in silico analyses, we anticipate that this work could be valuable to ongoing novel drug discovery with potential treatment for COVID-19.