Nipah virus is a pathogen considered highly infectious, and its lethality can cause between 40% and 70% of deaths in those infected. At present, no effective treatment is available which results in an imperative need to explore new approaches to the search for drugs. Through virtual screening techniques, docking and molecular dynamics, 183 ligands were evaluated against the Nipah virus glycoprotein (NiV-G), involved throughout the process of virus entry to the host cell, resulting in a good target for blocking the infection. Of the 183 drugs computationally screened, three of them (MMV020537, MMV688888 and MMV019838) were found to be potential inhibitors of NiV-G. Their calculated dissociation constants were 0.03 nM, 2.18 nM and 31.61 nM, respectively. Molecular dynamics studies confirm their stability binding modes in the active site of the protein. These potential inhibitors can be used later as leads for the development of new drugs that allow effective treatment of the disease. Communicated by Ramaswamy H. Sarma

Serine/threonine kinase 16 (STK 16) is involved in many facets of cellular regulation; activation of STK 16 plays a crucial role in the migration of cancer cells. Therefore, it is a novel target for the discovery of anticancer agents. Herein, virtual screening and dynamics simulation were used to screen a large library of natural compounds against STK 16 using Schrodinger suit 2021-2 and GROMACS 2021.6. The results predicted five molecules with high binding affinity against the target, with NPC132329 (Arcyriaflavin C) and NPC160898 having higher binding affinity and molecular mechanics generalized born surface area (MM/GBSA), suggesting that it is better than the standard inhibitor. The molecular dymanics (MD) simulation studies showed that the STK 16-NPC132329 complex has the lowest root mean square deviation, and STK 16-NPC160898 was the most stable compared with the standard drug and selective STK 16 inhibitor. The minimal fluctuation was observed in the STK 16-NPC132329 and STK 16-NPC160898 complexes based on the root mean square fluctuation trajectory with NPC132329 and NPC160898 forming 2 and 3 hydrogen bonds respectively with the amino acid residue of the target’s binding site. Overall, NPC132329 and NPC160898 are better STK 16 inhibitors than the standard drug and selective inhibitor, which can be further studied to discover novel anticancer drugs.

Gastric ulcer is associated with weakening of the mucous coating of the stomach and damages to the intestinal lining. It is caused by H. pylori assisted by enzymes including VacA, which necessitates the need for inhibitors of VacA. Bioactive compounds from Cyperus rotundus have been documented to have anti-inflammatory activities. However, the mechanism of action of the phytochemicals is not characterized. This research aimed to assess, in silico, the potential of selected bioactive compounds against VacA based on the binding to its active sites. VacA and bioactive compounds structures were obtained from protein database and PubChem webserver, respectively. All compounds, including 2 controls, omeprazole and cimetidine were docked against the protein using AutoDock Vina and screened based on the binding energy. The selected complexes were subjected to pharmacokinetics and toxicity screening. Finally, molecular dynamics simulation and MMPBSA were carried out on two best compounds. 17 compounds interacted with the active site of VacA with higher binding affinities, with 7 of them – aureusidine, catechin, chlorogenic acid, isorhamnetin, isovitexin, oreintin, and vitexin having the best behaviours based on ADMET and druglikeness screening. Molecular dynamics and MMPBSA experiments of two of the hits corroborated good stability and binding energy for Ellagic Acid and Scirpusin B (ΔG = −14.38 and −13.20 kcal mol⁻¹, respectively). These phytochemicals showed good pharmacokinetic profiles with respect to the control drugs. This study revealed that the identified compounds of C. rotundus may serve as VacA inhibitors and may be potent candidates for novel drug formulations in gastric ulcer treatment. Communicated by Ramaswamy H. Sarma