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. ARTICLE HISTORY

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 À17.90 ± 0.23, À18.21 ± 0.25, and À9.67 ± 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.

These in vitro studies investigated the comparative antiglycemic properties and molecular docking of the methanolic extracts of dried leaves of Ageratum conyzoides L. and Phyllanthus amarus L. in an attempt to explore natural products that could be useful in preventing secondary complications that could arise from hyperglycaemia. The methanolic crude extracts of dried leaves of A. conyzoides (CEA) and P. amarus (CEP) were partitioned into n-butanol and aqueous extracts and glycation inhibitory potentials were investigated. The result reveals that CEA and CEP exhibited highest glycemic inhibitory potential on the activities of α-amylase, α-glucosidase and sucrase investigated. The molecular docking was done on reported identified compounds in A. conyzoides and P. amarus with α-amylase (1SMD), sucrase-isomaltase (3LPO) and α-glucosidase (3WY1). Methanol crude extracts exhibited the highest inhibitory effect with the lowest IC 50 values

Background This study assessed the antiglycaemic properties of the methanolic extracts of the dried leaf of Cassia alata L. through in vitro and in silico approaches. The methanolic crude extract (MCE) of the dried leaf was prepared and partitioned into n-butanol (BPE) and aqueous (ARE) extracts. The antiglycaemic potential was assessed in vitro by studying the inhibitory actions of the extracts with α-amylase, α-glucosidase, and sucrase. The antiglycation capacity of the extracts was evaluated through the inhibition of albumin glycation, thiol oxidation, and β-fibril formation. Previously identified compounds (emodin, quercetin, chrysoeriol, and kaempferol) were docked with α-amylase (1HNY), α-glucosidase (5ZCB), and sucrase-isomaltase (3LPO) using the Pyrex Virtual Screening tool. Results The results revealed that MCE had the highest inhibitory potential with the lowest IC50 values of 69.67 ± 0.88, 65.54 ± 0.34, and 48.35 ± 1.45 μg/mL for α-amylase, α-glucosidase, and sucrase inhibitions, respectively. The molecular docking studies showed that quercetin and kaempferol had the best docking scores with 1HNY while emodin and chrysoeriol had the best scores towards 5ZCB and 3LPO. MCE and BPE significantly (p < 0.05) inhibited glucose-induced albumin glycation and modification. Conclusion This study suggested that the extract of the leaf of C. alata could contain a mix of different phytochemicals that could be beneficial in reducing the absorption of glucose and preventing diabetes-induced complications.

Background Cancer is responsible for high morbidity and mortality globally. Because the overexpression of histone deacetylases (HDACs) is one of the molecular mechanisms associated with the development and progression of some diseases such as cancer, studies are now considering inhibition of HDAC as a strategy for the treatment of cancer. In this study, a receptor-based in silico screening was exploited to identify potential HDAC inhibitors among the compounds isolated from Cajanus cajan, since reports have earlier confirmed the antiproliferative properties of compounds isolated from this plant. Results Cajanus cajan-derived phytochemicals were docked with selected HDACs, with givinostat as the reference HDAC inhibitor, using AutodockVina and Discovery Studio Visualizer, BIOVIA, 2020. Furthermore, absorption, distribution, metabolism and excretion (ADME) drug-likeness analysis was done using the Swiss online ADME web tool. From the results obtained, 4 compounds; betulinic acid, genistin, orientin and vitexin, were identified as potential inhibitors of the selected HDACs, while only 3 compounds (betulinic acid, genistin and vitexin) passed the filter of drug-likeness. The molecular dynamic result revealed the best level of flexibility on HDAC1 and HDAC3 compared to the wild-type HDACs and moderate flexibility of HDAC7 and HDAC8. Conclusions The results of molecular docking, pharmacokinetics and molecular dynamics revealed that betulinic acid might be a suitable HDAC inhibitor worthy of further investigation in order to be used for regulating conditions associated with overexpression of HDACs. This knowledge can be used to guide experimental investigation on Cajanus cajan-derived compounds as potential HDAC inhibitors.