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.

Exploring the Fatty Acid Binding Pocket in the SARS-CoV-2 Spike Protein – Confirmed and Potential Ligands

“…However, no favorable binding poses could be obtained for this compound using Glide SP, potentially indicating an inefficient interaction with the FABP . Likewise, although Psammaplysene D has been described to interact with some FABP residues (Ser373, Phe374), no favorable binding poses could be obtained using the Glide SP docking tool. , In the case of Psammaplysene D, the failure to obtain docking poses could be due to the larger size of the molecule, with a molecular weight of 783.2 g/mol, significantly surpassing confirmed ligands and likely not fitting the pocket properly. As for asiatic acid, taking into account the binding predicted for dexamethasone and bile acid derivatives, the absence of docking poses obtained is unexpected.…”

Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19

“…Plants have provided a promising alternative production platform for both natural bioactive compounds and recombinant therapeutics [ 31 ]. Plants naturally produce a diverse range of bioactive small molecules, such as alkaloids [ 32 ], flavonoids [ 33 ], terpenoids [ 34 ], and phenolic compounds [ 35 ], which are the source of countless pharmaceutical compounds for treating various diseases. Many bioactive compounds from medicinal plants, for example, those extracted from Artemisia annua L., Curcuma longa and Tripterygium wilfordii have been demonstrated to exhibit significant activities against SARS-CoV-2 through interfering with every step of the interaction of the virus with its host cells [ 36 , 37 ].…”

Identification of Potential Anti‐COVID‐19 Drug Leads from Medicinal Plants through Virtual High‐Throughput Screening

“…During the COVID‐19 pandemic, several herbal compound databases derived from the medicinal plants of various geographical regions, such as China, [65,69,73–76] India, [68,77] Vietnam, [78] Korea, [65] Jordan, [79] Africa, [80] and Brazil [81] have been evaluated, both computationally and experimentally, for their potential antiviral activities against the SARS‐CoV‐2. Accordingly, it has been reported that multiple phytochemicals from various compound classes, including polyphenols, [55,60,62–63,68,78,82–84] alkaloids, [57,63,66–69,85] terpenes [55,63,66–67,69,84,86] and flavonoids [9,55,60,63,66–69,71,76,82–84,87] show a striking antiviral activity against the virus.…”