The Main Protease of SARS-CoV-2 as a Target for Phytochemicals against Coronavirus

Abstract

In late December 2019, the first cases of COVID-19 emerged as an outbreak in Wuhan, China that later spread vastly around the world, evolving into a pandemic and one of the worst global health crises in modern history. The causative agent was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although several vaccines were authorized for emergency use, constantly emerging new viral mutants and limited treatment options for COVID-19 drastically highlighted the need for developing an efficient treatment for this disease. One of the most important viral components to target for this purpose is the main protease of the coronavirus (Mpro). This enzyme is an excellent target for a potential drug, as it is essential for viral replication and has no closely related homologues in humans, making its inhibitors unlikely to be toxic. Our review describes a variety of approaches that could be applied in search of potential inhibitors among plant-derived compounds, including virtual in silico screening (a data-driven approach), which could be structure-based or fragment-guided, the classical approach of high-throughput screening, and antiviral activity cell-based assays. We will focus on several classes of compounds reported to be potential inhibitors of Mpro, including phenols and polyphenols, alkaloids, and terpenoids.

Biophysical Interpretation of Evolutionary Consequences on the SARS-CoV2 Main Protease through Molecular Dynamics Simulations and Network Topology Analysis

“…Therefore, Mpro becomes one of the important targets for drug development against SARS-CoV2, 13−15 inspiring many X-ray crystallographic 11,16,17 and computational studies to search for either possible drug repurposing 18−22 or alternative immunity boosts from herbal extracts. 23 The structure of an Mpro as shown in Figure 1a consists of three domains: domains I (residues 15−99) and II (residues 1−14, 100−197) consist of antiparallel β-barrel structures, while domain III (residues 198−301) forms a compact αhelical domain connected to domain II by a long linker loop. The nomenclature for each α helix and β strand within each domain is also provided in Figure 1a along with the amino acid sequence.…”

“…The genome of SARS-CoV2 contains around 32 kb, in which two-third of the genome length is translated into polyproteins pp1a and pp1ab. , The nonfunctional polyproteins are processed by the 3C-like protease or the main protease (Mpro), along with one or two papain-like proteases, to provide 16 fully functional nonstructural proteins. Therefore, Mpro becomes one of the important targets for drug development against SARS-CoV2, − inspiring many X-ray crystallographic ,, and computational studies to search for either possible drug repurposing − or alternative immunity boosts from herbal extracts …”

Synthesis, SARS‐CoV‐2 3CL main protease inhibitor, anti‐inflammatory, and wound‐healing effects of a zinc(II)‐thiosemicarbazone complex

“…Phylogenetically, the amino acid sequence and 3D structure of the main protease (M pro ) are highly conserved throughout the subfamily Coronavirinae. [14,21] IL8 is a chemoattractant and an activator cytokine for neutrophils in the site of inflammation. [22] Tumor necrosis factor alpha (TNF-α), which induces IL8 cytokine, is important in almost all acute inflammatory reactions and acts as an inflammation promoter.…”

“…Phylogenetically, the amino acid sequence and 3D structure of the main protease (M pro ) are highly conserved throughout the subfamily Coronavirinae. [ 14,21 ]…”

A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19

“…VN contains secondary metabolites primarily flavonoids and terpenoids. These groups of compounds have shown promising effects against reduction of exacerbation in COVID-19 primarily by inhibiting SARS-CoV-2 Mpro [10][11][12].…”