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

Amr El-Demerdash,Afnan Hassan,James D. Stockand,Tarek Mohamed Abd El-Aziz,Reem K. Arafa

doi:10.3390/molecules26206171

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.

Highlights

A high throughput virtual screening of a library consisting of fourteen marine Brominated tyrosine alkaloids (BTAs), five bromotyrosine compounds with established antiviral properties (1–5, Figure 2), and nine bromotyrosine derivatives (6–14, Figure 3) from the French Polynesian marine sponge, Suberea ianthelliformis, was performed against five SARS-CoV-2 target proteins
The S-scores for all fourteen library compounds were greater for the spike glycoprotein
(−5.14 to −7.65 Kcal/mol) compared to the spike glycoprotein co-crystallized with a native ligand (S-score = −4.55 Kcal/mol), with compound 3 once more having the best predicted binding affinity (S-score = −7.65 Kcal/mol)

Summary

Introduction

The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted global health and economics [1]. The signs and symptoms of COVID-19 are grouped into three categories according to the severity of the infection and mortality: mild, severe, and critical. The majority of COVID-19 patients, 80%, experience mild symptoms and recover. Severe symptoms appear in 13.8% of cases and 6.1% become critically ill [2,3]

Methods

Results

Conclusion