| Autor: |
Abdel-moniem S. Hassan, Abdo A. Elfiky, Alaa M. Elgohary |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of King Saud University: Science, Vol 35, Iss 10, Pp 102923- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1018-3647 |
| DOI: |
10.1016/j.jksus.2023.102923 |
| Popis: |
Objectives: Mucormycosis has been reported associated with SARS-CoV-2 infections during the last year. The viral RNA-dependent RNA polymerase (RdRp) was proved to be a critical protein target in viral and fungal pathogens. The human inosine monophosphate dehydrogenase (IMPDH) is an evolved antiviral and antimicrobial therapeutic target. The aim is to triple-hit the viral and fungal RdRps and the human IMPDH. Methods: In the current study, molecular docking combined with molecular dynamics simulation (MDS) is utilized to test nucleotide inhibitors against the RdRps of SARS-CoV-2 and Rhizopus oryzae (the main causing agent of mucormycosis) RdRp. Additionally, the same inhibitors targeted the human Inosine monophosphate dehydrogenase (IMPDH). Results: The results reveal a comparable binding affinity of four nucleotide derivatives compared to remdesivir and sofosbuvir against both IMPDH and the RdRps of SARS-CoV-2 and Rhizopus oryzae. The binding affinities are calculated using different conformations of the RdRps after 100 ns MDS and trajectories clustering. Conclusions: The current study suggests the triple inhibition potential of four nucleotide inhibitors against SARS-CoV-2 & R. oryzae RdRps and the human IMPDH, while experimental validation is yet to be performed. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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