Marine algal antagonists targeting 3CL protease and spike glycoprotein of SARS-CoV-2: a computational approach for anti-COVID-19 drug discovery

Abstract

The COVID-19 pandemic has severely destructed human life worldwide, with no suitable treatment until now. SARS-CoV-2 virus is unprecedented, resistance against number of therapeutics and spreading rapidly with high mortality, which warrants the need to discover new effective drugs to combat this situation. This current study is undertaken to explore the antiviral potential of marine algal compounds to inhibit the viral entry and its multiplication using computational analysis. Among the proven drug discovery targets of SARS-CoV-2, spike glycoprotein and 3-chymotrypsin-like protease are responsible for the virus attachment and viral genome replication in the host cell. In this study, the above-mentioned drug targets were docked with marine algal compounds (sulfated polysaccharides, polysaccharide derivatives and polyphenols) using molecular docking tools (AutoDockTools). The obtained results indicate that κ-carrageenan, laminarin, eckol, trifucol and β-D-galactose are the top-ranking compounds showing better docking scores with SARS-CoV-2 targets, than the current experimental COVID-19 antiviral drugs like dexamethasone, remdesivir, favipiravir and MIV-150. Further, molecular dynamic simulation, ADMET and density functional theory calculations were evaluated to substantiate the findings. To the best of our knowledge, this is the first report on in silico analysis of aforesaid algal metabolites against SARS-CoV-2 targets. This study concludes that these metabolites can be curative for COVID-19 in the hour of need after further validations in in vitro and in vivo testings. Communicated by Ramaswamy H. Sarma

Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling

“…Our top-ranked compound of eugeniin (−9.8 kcal/mol), syzyginin B (−10.4 kcal/mol), eugenol (−7.3 kcal/mol), and casuarictin (−12.2 kcal/mol) has shown higher binding affinity than the commercially available drugs such as remdesivir (−6 kcal/mol), liponavir (−4 kcal/mol), tamiflu (−5.72 kcal/mol), plaquenil (−5.59 kcal/mol), and mycophenolic (−6.02 kcal/mol) ( Arunkumar et al, 2021 ; Khater and Nassar, 2021 ). Eugenol is extracted from cloves, is abundantly present in the clove oil, is used for antispasmodic treatment, and acts as a carminative to treat gastrointestinal disorders.…”

“…The structure was subjected to protein preparation using autodock tools, a graphical user interface program, which was exploited for the preparation, running, and analyzing the docking simulations. Water molecules, ligand groups (inhibitor), and other nonspecific molecules were removed, polar hydrogen was added with the merging nonpolar hydrogens, and partial charges were assigned ( Arunkumar et al, 2021 ). The grids are placed in the region that possesses the nature of an active site since grids direct the ligand toward the binding site ( Forli et al, 2016 ).…”

Sulfated Polysaccharides Derived from Hypnea valentiae and Their Potential of Antioxidant, Antimicrobial, and Anticoagulant Activities with In Silico Docking

“…Carrageenan had been exploited with antimicrobial, antiviral, and anticancer activity. The current research observed a significant interaction of the carrageenan with multiple targets resulting majorly around −7 to −6 Kcal/mol binding score [ 28 , 77 ].…”

“…Computational methods such as molecular docking have played a critical role in rationalizing the road to drug discovery in order to overcome these obstacles. A molecular docking feature becomes a promising pharmaceutical research tool for screening candidates from drug libraries effectively [ 28 ]. In such studies, the ultimate goal was to find effective therapeutics for the carrageenan molecule extracted from marine algae.…”

Evaluation of Nutritional Substances and Investigation of Antioxidant and Antimicrobial Potentials of Boerhavia diffusa with in Silico Molecular Docking

“…To overcome these barriers, computational approaches such as molecular docking have played a significant role in streamlining the road to drug development. The use of molecular docking technology in drug research is currently a valuable method for quickly screening candidates from drug libraries [3]. B. diffusa is commonly known as red spiderling or common hogweed.…”