The reemergence of coronavirus prompts the need for the development of effective therapeutics to prevent the cellular entry and replication of coronavirus. This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. The pharmacodynamic and pharmacokinetic properties were predicted through the pkCSM server while the corresponding binding affinity of the selected drugs towards the proteins was computed using AutodockVina Screening tool. The ADMET properties revealed all the drugs possess drug-like properties. Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex. Moreover, it was also observed that chloroquine has appreciable binding affinities for 3-Chymotrpsin- like protease and cyclic AMP-dependent protein kinase A when compared to Oseltamivir and ribavirin. The study provided evidence suggesting putative repurposing of the selected drugs for the development of valuable drugs for the prevention of cellular entry and replication of coronavirus.

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of −17.90 ± 0.23, −18.21 ± 0.25, and −9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication. Communicated by Ramaswamy H. Sarma

The investigation and knowledge of calcium handling mechanisms in the plasmodium has been considered as a potential biological target against malaria. This study deals with the evaluation of inhibitory activity of secondary metabolites of ethylacetate partitioned-fraction of Adansonia digitata stem bark extract on malaria-associated protein using in silico docking studies. Molecular docking and virtual screening was performed to understand the mechanism of ligand binding and to identify potent calcium transporter inhibitors. The stem bark extracts of A. digitata contains rich sources of phytochemicals. The secondary metabolites were determined by HPLC-DAD and HRGC-MS analysis. The major chemical constituent present in the ethylacetate partitioned-fraction of A. digitata stem bark extract were examined for their antiplasmodial activity and were also involved in docking study. The secondary metabolites, quercetin and apigenin inhibited the formation of β-hematin. The results showed that all the selected compounds in the A. digitata showed binding energy ranging between -6.5 kcal/mol and -7.1 kcal/mol. Among the two chemical constituents, apigenin has the highest docking score along with the highest number of hydrogen bonds formed when compared to quercetin. Analysis of the results suggests that apigenin and quercetin could act as an anti-malaria agent. Molecular docking analysis could lead to further development of potent calcium transporter inhibitors for the prevention and treatment of malaria and related conditions.