Polyphenolic Natural Products Active In Silico Against SARS-CoV-2 Spike Receptor Binding Domains and Non-structural Proteins - A Review

Abstract

: The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus’ high transmissibility. With the emergence of new variants, this global phenomenon took on a more dramatic turn with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.

Virtual Screening of Cyanobacterial Metabolites as Inhibitors of SARS-CoV-2 Host Cell Entry, Viral Replication, and Host Immunity Modulation Infective Mechanisms

“…Two target protein sites important for infectivity (spike RBDs for ACE2 and GRP78) and three non-structural proteins of SARS-CoV-2 (RdRp, 3CL PRO , and PL PRO ) were chosen as molecular targets. The three-dimensional crystal structures of the following target proteins were retrieved from the RCSB protein data bank (RCSB.org): spike's receptor-binding domain (RBD) for ACE2 (PDB ID: 6M0J) and GRP78 (PDB ID: 6VXX), RdRp (PDB ID: 6M71), 3CL PRO (PDB ID: 6LU7), and PL PRO (PDB ID: 6W9C) (Brogi et al 2022;Fernandez et al 2021;Quimque et al 2021a;Lan et al 2020;Walls et al 2020;Gao et al 2020;Jin et al 2020;Osipiuk et al 2020). PDB structures were retrieved based on previous publications, prioritizing high resolution and comparability of results (Africa et al 2022;de Leon et al 2021;Fernandez et al 2021).…”

“…The use of CADDD (computer-aided drug design and discovery) has accelerated drug development to streamline efforts in the discovery of compounds for in vitro and in vivo experimental studies (Chaudhary and Mishra 2016). Among the numerous in silico techniques is molecular docking, which is commonly used in the discovery for treatment against SARS-CoV-2 (de Leon et al Fernandez et al 2021;Quimque et al 2021a). With this, virtual screening streamlines secondary metabolites as drug leads with biological activities against SARS-CoV-2 (Brogi et al 2022;Chaudhary and Mishra 2016;Quimque et al 2021a).…”

“…Among the numerous in silico techniques is molecular docking, which is commonly used in the discovery for treatment against SARS-CoV-2 (de Leon et al Fernandez et al 2021;Quimque et al 2021a). With this, virtual screening streamlines secondary metabolites as drug leads with biological activities against SARS-CoV-2 (Brogi et al 2022;Chaudhary and Mishra 2016;Quimque et al 2021a).…”

Virtual Combinatorial Library Screening of Quinadoline B Derivatives against SARS-CoV-2 RNA-Dependent RNA Polymerase

“…In COVID-19 drug discovery, several possible drug targets, comprising structural and non-structural proteins, have been exploited in searching novel chemical entities as anti-SARS-CoV-2 agents [10][11][12][13]. Among these targets is the RNA-dependent RNA polymerase (RdRp), which is a multi-domain SARS-CoV-2 protein playing a crucial role in the viral life cycle.…”

Combinatorial library screening of quinadoline B derivatives against SARS-CoV-2 RNA-dependent RNA polymerase

“…In COVID-19 drug discovery, several possible drug targets, comprised structural and non-structural proteins, have been exploited in searching novel chemical entities as anti-SARS-CoV-2 agents [10][11][12][13]. Among these targets is the RNA-dependent RNA polymerase (RdRp), which is a multi-domain SARS-CoV-2 protein playing a crucial role in the viral life cycle.…”