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.
ABSTRACT
This work deals with the synthesis, crystal structure, computational study and antiviral potential of mixed ligand copper(II) complex [Cu(L)(phen)](1), (where, H2L = (Z)-N'-((E)-2-hydroxy-3,5-diiodobenzylidene)-N,N-dimethylcarbamohydrazonothioic acid, phen = 1,10-phenanthroline). The Schiff base ligand (H2L) is coordinated with Cu(II) ion in O, N, S-tridentate mode. The copper complex (1) crystallized in the monoclinic system of the space group P21/c with eight molecules in the unit cell and reveals a square pyramidal geometry. Furthermore, we also perform quantum chemical calculations to get insights into the structure-property relationship and functional properties of ligand (H2L) and its copper (II) complex [Cu(L)(phen)](1). Complex [Cu(L)(phen)](1) was also virtually designed in-silico evaluation by Swiss-ADME. Additionally, inspiring by recent developments to find a potential inhibitor for the COVID-19 virus, we have also performed molecular docking study of ligand and its copper complex (1) to see if our compounds shows an affinity for the main protease (Mpro) of COVID-19 spike protein (PDB ID: 7C8U). Interestingly, the results are found quite encouraging where the binding affinity and inhibition constant were found to be -7.14 kcal/mol and 5.82 µM for ligand (H2L) and -6.18 kcal/mol and 0.76 µM for complex [Cu(L)(phen)](1) with Mpro protein. This binding affinity is reasonably well as compared to recently known antiviral drugs. For instance, the binding affinity of ligand and complex was found to be better than docking results of chloroquine (-6.293 kcal/mol), hydroxychloroquine (-5.573 kcal/mol) and remdesivir (-6.352 kcal/mol) with Mpro protein. The present study may offer the technological solutions and potential inhibition to the COVID-19 virus in the ongoing and future challenges of the global community. In the framework of synthesis and characterization of mixed ligand copper (II) complex; the major conclusions can be drawn as follow.