Target prediction, computational identification, and network-based pharmacology of most potential phytoconstituent in medicinal leaves of Justicia adhatoda against SARS-CoV-2.

The current global epidemic of the novel coronavirus (SARS-CoV-2) has been labeled a global public health emergency since it is causing substantial morbidity and mortality on daily basis. We need to identify an effective medication against SARS-CoV-2 because of its fast dissemination and re-emergence. This research is being carried out as part of a larger strategy to identify the most promising therapeutic targets using protein-protein interactions analysis. Mpro has been identified as one of the most important therapeutic targets. In this study, we did in-silico investigations to identify the target and further molecular docking, ADME, and toxicity prediction were done to assess the potential phyto-active antiviral compounds from Justicia adhatoda as powerful inhibitors of the Mpro of SARS-COV-2. We also investigated the capacity of these molecules to create stable interactions with the Mpro using 100 ns molecular dynamics simulation. The highest scoring compounds (taraxerol, friedelanol, anisotine, and adhatodine) were also found to exhibit excellent solubility and pharmacodynamic characteristics. We employed MMPBSA simulations to assess the stability of docked molecules in the Mpro binding site, revealing that the above compounds form the most stable complex with the Mpro. Network-based Pharmacology suggested that the selected compounds have various modes of action against SARS-CoV-2 that include immunoreaction enrichment, inflammatory reaction suppression, and more. These findings point to a promising class of drugs that should be investigated further in biochemical and cell-based studies to see their effectiveness against nCOVID-19.Communicated by Ramaswamy H. Sarma.

Tuberculosis and HIV responses threatened by nCOVID-19: A situation prompting an in silico investigation of reported MbtA inhibitors for combined inhibition of SARS-CoV-2 and HIV-TB co-infection

The menace of infectious diseases has constantly been a reason of concern for humankind since time immemorial. As evident by the name, infectious diseases can infect a huge population within a short period, leading to an eruption of pandemics and epidemics. The present human era is fortunate enough to have a wide array of readily available drugs that help cure and prevent various diseases. Moreover, the scientific community has always responded to the needs of society through its drug discovery and development programs. The co-existence of multiple diseases calls forth the scientific community to design and develop drugs that could have a broad spectrum of activity. In this perspective, our goal was to investigate the potential of reported MbtA inhibitors (antitubercular molecules) in inhibiting HIV-1 RT and nCovid-19-RdRp and eventually leading to the identification of a multi-targeted ligand (triple co-infection inhibitor). In this study, the primary success was attained by capitalizing on the structure-based virtual screening drug discovery approach. Results were quite promising. Molecular docking results showed that GV17 interacted strongly with the active site residues of both the target proteins (HIV-1 RT and nCOVID-19-RdRp). Moreover, the docking score of GV17 was more than that of the internal ligands of both the target proteins, which indicates a firm binding. Molecular dynamics further validated these results as identical amino acid residues were observed in the protein's docked pose with the ligand. The detailed atomic interactions of ligand GV17 with the protein residues have been discussed. Overall, the protein–ligand complexes remained stable throughout the simulation, and the system's backbone fluctuations were modest. MM-GBSA analysis revealed free binding energy of − 72.30 ± 7.85 kcal/mol and − 65.40 ± 7.25 kcal/mol for 1RT2 and 7BV2, respectively. The more negative binding energy indicates a stronger affinity of GV17 with both the receptors. GV17 also gave satisfactory predictive in silico ADMET results. Overall, this computational study identified GV17 as a potential HIT molecule and findings can open up a new avenue to explore and develop inhibitors against nCOVID-19-HIV-TB triple-infections.

Tuberculosis and HIV responses threatened by nCOVID-19: A situation prompting an in silico investigation of reported MbtA inhibitors for combined inhibition of SARS-CoV-2 and HIV-TB co-infection

The menace of infectious diseases has constantly been a reason of concern for humankind since time immemorial. As evident by the name, infectious diseases can infect a huge population within a short period, leading to an eruption of pandemics and epidemics. The present human era is fortunate enough to have a wide array of readily available drugs that help cure and prevent various diseases. Moreover, the scientific community has always responded to the needs of society through its drug discovery and development programs. The co-existence of multiple diseases calls forth the scientific community to design and develop drugs that could have a broad spectrum of activity. In this perspective, our goal was to investigate the potential of reported MbtA inhibitors (antitubercular molecules) in inhibiting HIV-1 RT and nCovid-19-RdRp and eventually leading to the identification of a multi-targeted ligand (triple co-infection inhibitor). In this study, the primary success was attained by capitalizing on the structure-based virtual screening drug discovery approach. Results were quite promising. Molecular docking results showed that GV17 interacted strongly with the active site residues of both the target proteins (HIV-1 RT and nCOVID-19-RdRp). Moreover, the docking score of GV17 was more than that of the internal ligands of both the target proteins, which indicates a firm binding. Molecular dynamics further validated these results as identical amino acid residues were observed in the protein’s docked pose with the ligand. The detailed atomic interactions of ligand GV17 with the protein residues have been discussed. Overall, the protein–ligand complexes remained stable throughout the simulation, and the system’s backbone fluctuations were modest. MM-GBSA analysis revealed free binding energy of − 72.30 ± 7.85 kcal/mol and − 65.40 ± 7.25 kcal/mol for 1RT2 and 7BV2, respectively. The more negative binding energy indicates a stronger affinity of GV17 with both the receptors. GV17 also gave satisfactory predictive in silico ADMET results. Overall, this computational study identified GV17 as a potential HIT molecule and findings can open up a new avenue to explore and develop inhibitors against nCOVID-19-HIV-TB triple-infections. [ FROM AUTHOR] Copyright of Structural Chemistry is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Flavonoids as potential therapeutics against novel coronavirus disease-2019 (nCOVID-19).

Since time immemorial natural products have been a great source of medicine to mankind. The anti-viral activities from several ayurvedic herbal medicines (in the form of crude extract or fraction or isolated compounds) have been established but their effectiveness against coronavirus still needs to be explored. They can provide a rich resource of anti-SARS-CoV-2 drug candidates. In this paper, in-silico techniques have been used to identify the potential lead molecules against SARS-CoV-2. A list of flavonoids having anti-viral activity was prepared and evaluated against the selected target. Rhoifolin, 5,7-dimethoxyflavanone-4'-O-ß-d-glucopyranoside, baicalin, astragalin, luteolin, and kaempferol showed good binding affinity and thus these could be promising compounds. In-silico screening such as ADMET prediction has been performed which predicted that the selected flavonoids have good pharmacokinetics and pharmacodynamics properties. Molecular dynamics simulation studies and MM-PBSA binding free energy calculations showed luteolin to be a more effective candidate against viral protein Mpro. The novelty of the approach mainly rests in the identification of potent anti-viral natural molecules from natural products flavonoid group of molecules to be effective against the latest coronavirus infection.Communicated by Ramaswamy H. Sarma.