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Elgohary, Alaa M., Elfiky, Abdo A., Pereira, Florbela, Abd El-Aziz, Tarek Mohamed, Sobeh, Mansour, Arafa, Reem K. and El-Demerdash, Amr 
ORCID: https://orcid.org/0000-0001-6459-2955
(2022)
Investigating the structure-activity relationship of marine polycyclic batzelladine alkaloids as promising inhibitors for SARS-CoV-2 main protease (Mpro).
Computers in Biology and Medicine, 147.
ISSN 0010-4825
Abstract
Over a span of two years ago, since the emergence of the first case of the novel coronavirus (SARS-CoV-2) in China, the pandemic has crossed borders causing serious health emergencies, immense economic crisis and impacting the daily life worldwide. Despite the discovery of numerous forms of precautionary vaccines along with other recently approved orally available drugs, yet effective antiviral therapeutics are necessarily needed to hunt this virus and its variants. Historically, naturally occurring chemicals have always been considered the primary source of beneficial medications. Considering the SARS-CoV-2 main protease (Mpro) as the duplicate key element of the viral cycle and its main target, in this paper, an extensive virtual screening for a focused chemical library of 15 batzelladine marine alkaloids, was virtually examined against SARS-CoV-2 main protease (Mpro) using an integrated set of modern computational tools including molecular docking (MDock), molecule dynamic (MD) simulations and structure-activity relationships (SARs) as well. The molecular docking predictions had disclosed four promising compounds including batzelladines H–I (8–9) and batzelladines F-G (6–7), respectively according to their prominent ligand-protein energy scores and relevant binding affinities with the (Mpro) pocket residues. The best two chemical hits, batzelladines H–I (8–9) were further investigated thermodynamically though studying their MD simulations at 100 ns, where they showed excellent stability within the accommodated (Mpro) pocket. Moreover, SARs studies imply the crucial roles of the fused tricyclic guanidinic moieties, its degree of unsaturation, position of the N–OH functionality and the length of the side chain as a spacer linking between two active sites, which disclosed fundamental structural and pharmacophoric features for efficient protein-ligand interaction. Such interesting findings are greatly highlighting further in vitro/vivo examinations regarding those marine natural products (MNPs) and their synthetic equivalents as promising antivirals.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: We thank ChemAxon Ltd. for access to JChem and Marvin. Shaheen supercomputer of King Abdullah University of Science and Technology (KAUST) was utilized for MD simulation calculations (under the project number k1482). Funding Information: Amr El-Demerdash is immensely grateful to the John Innes Centre, Norwich Research Park, United Kingdom for the postdoctoral fellowship. Florbela Pereira would like to thank Fundacão para a Ciência e a Tecnologia, MCTES, in the scope of the project UIDB/50006/2020 of the Research Unit, Associate Laboratory for Green Chemistry, LAQV". Publisher Copyright: © 2022 Elsevier Ltd |
| Uncontrolled Keywords: | batzelladines,guanidine alkaloids,marine sponges,molecular docking,molecular dynamics,sars,sars-cov-2,health informatics,computer science applications,sdg 3 - good health and well-being,sdg 14 - life below water ,/dk/atira/pure/subjectarea/asjc/2700/2718 |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 12 Aug 2024 17:30 |
| Last Modified: | 03 Sep 2024 08:00 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96208 |
| DOI: | 10.1016/j.compbiomed.2022.105738 |
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