Author:
Al-Karmalawy Ahmed A.,Dahab Mohammed A.,Metwaly Ahmed M.,Elhady Sameh S.,Elkaeed Eslam B.,Eissa Ibrahim H.,Darwish Khaled M.
Abstract
The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.
Cited by
129 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Design, synthesis, in vitro acetylcholinesterase, butyrylcholinesterase activities, and in silico molecular docking study of oxindole-oxadiazole hybrid analogues;Journal of Molecular Structure;2024-03
2. Synthesis, in vitro acetylcholinesterase, butyrylcholinesterase activities and molecular docking study of 1,3-oxathiol-2-imine derivatives;Chemical Data Collections;2024-03
3. Eco-friendly synthesis, structural elucidation, computational investigation and in vitro antioxidant activity of a new N-tosylated benzimidazole derivative;Journal of Molecular Structure;2024-01
4. Simulation of vitamin C derivatives as antioxidant using molecular docking;PROCEEDINGS OF THE 2ND INTERNATIONAL INTERDISCIPLINARY SCIENTIFIC CONFERENCE “DIGITALIZATION AND SUSTAINABILITY FOR DEVELOPMENT MANAGEMENT: ECONOMIC, SOCIAL, AND ENVIRONMENTAL ASPECTS”;2024
5. Characterization of lignin and hemicellulose degrading bacteria isolated from cow rumen and forest soil: Unveiling a novel enzymatic model for rice straw deconstruction;Science of The Total Environment;2023-12