Virtual screening of Microalgal compounds as potential inhibitors of Type 2 Human Transmembrane serine protease (TMPRSS2)

TL;DR

This study used computational methods to identify microalgal compounds as potential inhibitors of TMPRSS2, a key enzyme for SARS-CoV-2 entry, revealing promising candidates for COVID-19 therapeutic development.

Contribution

It presents the first in-silico screening of microalgal compounds targeting TMPRSS2, identifying potential inhibitors with favorable binding and pharmacokinetic profiles.

Findings

17 compounds showed strong binding affinity to TMPRSS2

Top 4 compounds have good pharmacokinetic and toxicity profiles

Microalgal compounds could serve as potential SARS-CoV-2 inhibitors

Abstract

More than 198 million cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported that result in no fewer than 4.2 million deaths globally. The rapid spread of the disease coupled with the lack of specific registered drugs for its treatment pose a great challenge that necessitate the development of therapeutic agents from a variety of sources. In this study, we employed an in-silico method to screen natural compounds with a view to identify inhibitors of the human transmembrane protease serine type 2 (TMPRSS2). The activity of this enzyme is essential for viral access into the host cells via angiotensin-converting enzyme 2 (ACE-2). Inhibiting the activity of this enzyme is therefore highly crucial for preventing viral fusion with ACE-2 thus shielding SARS-CoV-2 infectivity. 3D model of TMPRSS2 was constructed using I-TASSER, refined by GalaxyRefine, validated by Ramachandran plot server and overall model quality was checked by ProSA. 95 natural compounds from microalgae were virtually screened against the modeled protein that led to the identification 17 best leads capable of binding to TMPRSS2 with a good binding score comparable, greater or a bit lower than that of the standard inhibitor (camostat). Physicochemical properties, ADME (absorption, distribution, metabolism, excretion) and toxicity analysis revealed top 4 compounds including the reference drug with good pharmacokinetic and pharmacodynamic profiles. These compounds bind to the same pocket of the protein with a binding energy of -7.8 kcal/mol, -7.6 kcal/mol, -7.4 kcal/mol and -7.4 kcal/mol each for camostat, apigenin, catechin and epicatechin respectively. This study shed light on the potential of microalgal compounds against SARS-CoV-2. In vivo and invitro studies are required to developed SARS-CoV-2 drugs based on the structures of the compounds identified in this study.