Affiliation:
1. Department of Parasitology Noguchi Memorial Institute for Medical Research College of Health Sciences University of Ghana, Legon Accra Ghana
2. Technological University of Shannon: Midlands Midwest Midlands Campus Athlone Ireland
3. Department of Microbiology and Immunology School of Medical Sciences College of Health and Allied Sciences University of Cape Coast Cape Coast Ghana
4. UCD Conway Institute of Biomolecular and Biomedical Research School of Medicine University College Dublin Belfield D04 V1 W8 Ireland
5. Discipline of Pharmaceutical Sciences School of Health Sciences University of KwaZulu-Natal, Westville Campus Durban 4001 South Africa
6. West African Centre for Computational Research and Innovation Ghana
7. Department of Biochemical Engineering and Biotechnology Indian Institute of Technology-Delhi New Delhi, Delhi India
Abstract
AbstractNeuropilin 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.
Subject
Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering