Dieckol and Its Derivatives as Potential Inhibitors of SARS-CoV-2 Spike Protein (UK Strain: VUI 202012/01): A Computational Study
| Autor: | Bachir Yahia Khelif, Adil Alshoaibi, Ghazala Muteeb, Mohammad Aatif, Abdulrahman A. Alsultan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene Expression Regulation
Viral QH301-705.5 In silico 030303 biophysics Pharmaceutical Science Computational biology medicine.disease_cause spike protein Article Hydrophobic effect 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Drug Discovery medicine natural compounds Computer Simulation Homology modeling Biology (General) Pharmacology Toxicology and Pharmaceutics (miscellaneous) 030304 developmental biology Benzofurans 0303 health sciences Mutation Virtual screening Molecular Structure SARS-CoV-2 Binding potential COVID-19 Dieckol molecular docking and simulation seaweeds chemistry marine-derived compounds Spike Glycoprotein Coronavirus |
| Zdroj: | Marine Drugs, Vol 19, Iss 242, p 242 (2021) Marine Drugs Volume 19 Issue 5 |
| ISSN: | 1660-3397 |
| Popis: | The high risk of morbidity and mortality associated with SARS-CoV-2 has accelerated the development of many potential vaccines. However, these vaccines are designed against SARS-CoV-2 isolated in Wuhan, China, and thereby may not be effective against other SARS-CoV-2 variants such as the United Kingdom variant (VUI-202012/01). The UK SARS-CoV-2 variant possesses D614G mutation in the Spike protein, which impart it a high rate of infection. Therefore, newer strategies are warranted to design novel vaccines and drug candidates specifically designed against the mutated forms of SARS-CoV-2. One such strategy is to target ACE2 (angiotensin-converting enzyme2)–Spike protein RBD (receptor binding domain) interaction. Here, we generated a homology model of Spike protein RBD of SARS-CoV-2 UK strain and screened a marine seaweed database employing different computational approaches. On the basis of high-throughput virtual screening, standard precision, and extra precision molecular docking, we identified BE011 (Dieckol) as the most potent compounds against RBD. However, Dieckol did not display drug-like properties, and thus different derivatives of it were generated in silico and evaluated for binding potential and drug-like properties. One Dieckol derivative (DK07) displayed good binding affinity for RBD along with acceptable physicochemical, pharmacokinetic, drug-likeness, and ADMET properties. Analysis of the RBD–DK07 interaction suggested the formation of hydrogen bonds, electrostatic interactions, and hydrophobic interactions with key residues mediating the ACE2–RBD interaction. Molecular dynamics simulation confirmed the stability of the RBD–DK07 complex. Free energy calculations suggested the primary role of electrostatic and Van der Waals’ interaction in stabilizing the RBD–DK07 complex. Thus, DK07 may be developed as a potential inhibitor of the RBD–ACE2 interaction. However, these results warrant further validation by in vitro and in vivo studies. |
| Databáze: | OpenAIRE |
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