Dieckol and Its Derivatives as Potential Inhibitors of SARS-CoV-2 Spike Protein (UK Strain: VUI 202012/01): A Computational Study

Marine Drugs

Abdulrahman Alsultan¹  Ghazala Muteeb²  Adil Alshoaibi³  Mohammad Aatif⁴  BachirYahia Khelif⁴ 

[1] Department of Biomedical Sciences, College of Applied Medical Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia;Department of Nursing, College of Applied Medical Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia;Department of Physics, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia;Department of Public Health, College of Applied Medical Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia;

关键词: COVID-19;    natural compounds;    marine-derived compounds;    molecular docking and simulation;    seaweeds;    spike protein;   

DOI  :  10.3390/md19050242

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown