Computational Screening of Neuropilin-1 Unveils Novel Potential Anti-SARS-CoV-2 Therapeutics.

Neuropilin 1 (NRP-1) inhibition has shown promise in reducing the infectivity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and preventing the virus entry into nerve tissues, thereby mitigating neurological symptoms in COVID-19 patients. In this study, we employed virtual screening, including molecular docking, Molecular Dynamics (MD) simulation, and Molecular Mechanics-Poisson Boltzmann Surface Area (MM-PBSA) calculations, to identify potential NRP-1 inhibitors. From a compendium of 1930 drug-like natural compounds, we identified five potential leads: CNP0435132, CNP0435311, CNP0424372, CNP0429647, and CNP0427474, displaying robust binding energies of -8.2, -8.1, -10.7, -8.2, and -8.2 kcal/mol, respectively. These compounds demonstrated interactions with critical residues Tyr297, Trp301, Thr316, Asp320, Ser346, Thr349, and Tyr353 located within the b1 subdomain of NRP-1. Furthermore, MD simulations and MM-PBSA calculations affirmed the stability of the complexes formed, with average root mean square deviation, radius of gyration, and solvent accessible surface area values of 0.118 nm, 1.516 nm, and 88.667 nm2 , respectively. Notably, these lead compounds were estimated to penetrate the blood-brain barrier and displayed antiviral properties, with Pa values ranging from 0.414 to 0.779. The antagonistic effects of these lead compounds merit further investigation, as they hold the potential to serve as foundational scaffolds for the development of innovative therapeutics aimed at reducing the neuroinfectivity of SARS-CoV-2.

An In vitro and in silico investigation of the antitrypanosomal activities of the stem bark extracts of Anopyxis klaineana (Pierre) Engl.

African Trypanosomiasis caused by trypanosome parasites continues to be a major neglected health problem, particularly in developing countries. Current treatments are marked by serious side effects, low effectiveness, high toxicity, and drug resistance prompting the need to develop novel, safe, effective, and alternative antitrypanosomal compounds. Anopyxis klaineana is an ethnomedicinal plant used in West Africa to treat many ailments including protozoan diseases. In this study, we investigated the antitrypanosomal potential of stem bark extracts of A. klaineana through in vitro and in silico approaches. A. klaineana extracts were tested for their antitrypanosomal activities against Trypanosoma brucei parasite in vitro using Alamar blue assay. In addition, the antioxidant and cytotoxic activities were determined. LC-ESI-QTOF-MS was used to identify potential bioactive compounds present in the A. klaineana extracts. Bioactive compounds identified were subjected to molecular docking studies against Trypanosoma brucei's trypanothione reductase (TR) and Uridine Diphosphate Galactose 4'-Epimerase (UDP). The A. klaineana extracts (methanol, hexane, chloroform, and ethyl acetate) exhibited potential anti-trypanosomal activities with IC50 values of 21.25 ± 0.755,4.35 ± 0.166,2.57 ± 0.153 and 22.92 ± 2.321 µg/mL respectively. Moreover, the methanolic crude extracts showed moderate cytotoxicity against HepG2 and PNT2 cells, with IC50 values of 68.0 ± 2.05 and 78.7 ± 2.63 µg/mL respectively. LC-MS analysis revealed the presence of 24 bioactive compounds with 5 being druglike. Risperidone, Ranolazine, Dihydro-7-Desacetyldeoxygedunin, 6 beta-Hydroxytriamcinolone acetonide, and Dimethylmatairesinol were identified as novel potential inhibitors of TR and UDP with binding affinities of -10.4, -7.9, -8.7, -8.4 and -7.1 kcal/mol respectively against TR and -10.8, -8.4, -8.4, -7.6 and -8.1 respectively against UDP. This study indicates that A. klaineana has potential antitrypanosomal properties and therefore may have the potential to be developed as a therapeutic intervention for treating African trypanosomiasis.