Probing marine brown macroalgal phlorotannins as antiviral candidate against SARS-CoV-2: molecular docking and dynamics simulation approach.

Over the past year, owing to the emergent demand for the search for potential COVID-19 therapeutics, identifying alternative candidates from biological sources is one of the sustainable ways to reinforce the drug discovery process. Marine macroalgae have numerous advantages because of the richest availability of underexploited bioactive compounds. Polyphenolic compounds like phlorotannins obtained from brown macroalgae are reported as proven antiviral and immunostimulatory agents. Thus, the present study evaluated the possibility of phlorotannins as antagonists to the multiple target proteins essential for SARS-CoV-2 replication. Twenty different types of potent phlorotannins were targeted against druggable target proteins, viz., 3CLpro, RdRp, and Spro using AutoDock molecular docking, drug-likeness were assessed by ADMET profiling (QikProp module). Further, validated with 200 ns molecular dynamics (MD) simulation (Desmond module) for the top-ranked phlorotannins based on docking binding affinities. Among the twenty phlorotannins studied, eckol hexacetate, phlorofucofuroeckol, fucofuroeckol, and bifuhalol-hexacetate showed significant binding affinities across the selected targets. Besides, MD simulations highlighted Glu166, Gln189, Cys145, and Thr190 tetrad as potential interaction sites to inhibit 3CLpro's activity. Moreover, phlorotannins were confirmed to be druglike, with no major deviation observed in ADMET-profiling. Hence, phlorotannins could be therapeutic candidates against SARS-CoV-2. However, further investigations are needed to prove its efficacy as an antiviral agent. Conclusively, this study may envisage that the novel finding could notably impact the advancement of antiviral interventions for COVID-19 in the near future.

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

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 ß-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.