Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2.

ABSTRACT

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people. Despite the availability of a number of vaccines which provide protection against this virus, the evolution of new viral variants, inconsistent availability of the vaccine around the world, and vaccine hesitancy, in some countries, makes it unreasonable to rely on mass vaccination alone to combat this pandemic. Consequently, much effort is directed to identifying potential antiviral treatments. Marine brominated tyrosine alkaloids are recognized to have antiviral potential. We test here the antiviral capacity of fourteen marine brominated tyrosine alkaloids against five different target proteins from SARS-CoV-2, including main protease (Mpro) (PDB ID 6lu7), spike glycoprotein (PDB ID 6VYB), nucleocapsid phosphoprotein (PDB ID 6VYO), membrane glycoprotein (PDB ID 6M17), and non-structural protein 10 (nsp10) (PDB ID 6W4H). These marine alkaloids, particularly the hexabrominated compound, fistularin-3, shows promising docking interactions with predicted binding affinities (S-score = -7.78, -7.65, -6.39, -6.28, -8.84 Kcal/mol) for the main protease (Mpro) (PDB ID 6lu7), spike glycoprotein (PDB ID 6VYB), nucleocapsid phosphoprotein (PDB ID 6VYO), membrane glycoprotein (PDB ID 6M17), and non-structural protein 10 (nsp10) (PDB ID 6W4H), respectively, where it forms better interactions with the protein pockets than the native interaction. It also shows promising molecular dynamics, pharmacokinetics, and toxicity profiles. As such, further exploration of the antiviral properties of fistularin-3 against SARS-CoV-2 is merited.