Inhibition of S-protein RBD and hACE2 Interaction for Control of SARSCoV- 2 Infection (COVID-19)

Abstract

Background: COVID-19 has become pandemic with higher morbidity and mortality rates after its start from Wuhan city of China. The infection by RNA virus, also known as SARS-CoV-2 or 2019-nCoV, from beta class of corona viruses has been found to be responsible for COVID-19. Structural analysis and evidences have been indicated that interaction between a segment of receptor binding domain (RBD) from S protein of virus and human angiotensin-converting enzyme 2 (hACE2) is essential for cellular entry of virus. Objective: The current review put the light on structural aspects for inhibition of RBD-hACE2 interaction mediated cellular entry of SARS-CoV-2. Methods: The present study provides a critical review of recently published information on RBD-hACE2 interaction and its inhibitors to control SARS-CoV-2 infection. The review highlighted the structural aspects of interaction between RBDhACE2 and involved amino acid residues. Results: Recently, several studies are being conducted for inhibition of the SARS-CoV-2 attachment and entry to the human cellular system. One of the important targets for viral invasion is its binding with cell surface receptor, hACE2, through RBD on S-protein. Mimicking of three residues on ACE2 (Lys31, Glu35 and Lys353 on B chain) provided hot target directed strategy for inhibition of early attachment of virus to the cell. Early screening of peptidic or non-peptidic molecules for inhibition of RBD-hACE2 interaction has been raised the hope for potential therapeutics against COVID-19. The higher affinity of molecules toward RBD than ACE2 is important factor for selectivity and minimization of ACE2 related adverse events on cardiovascular system, brain, kidney, and foetus development during pregnancy. Conclusion: Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for control of SARS-CoV-2 infection. Recently, published reports pointed out Lys31, Glu35 and Lys353 on B chain of ACE2 as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells. Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding pattern and potencies (IC50 values) which will help for further improvement in the selectivity.

Graphene oxide and flavonoids as potential inhibitors of the spike protein of SARS-CoV-2 variants and interaction between ligands: a parallel study of molecular docking and DFT

“…This must occur because the Omicron variant presents several modifications on its structure including on RBD which increases its transmission capacity [49]. The binding affinity reached for apigenin is in accordance with the studies of Subbaiyan (2020) [50] and also with the values reached for polyphenols catechin and curcumin [51] and for other flavonoids, which presented the affinity binding values from −11.2 to −8.0 kcal/mol against spike protein [52].…”

Molecular modeling of the interaction of ligands with ACE2–SARS-CoV-2 spike protein complex

“…In this context, molecular modeling remains relevant as a predictor to evaluate binding of ligands such as ACE inhibitors or other current medications as potential repurposed therapeutics to target proteins or enzymes involved during viral infection caused by the emerging variants (Xu et al 2020;Nayak 2021;Suryamohan et al 2021;Acharya et al 2020;Narkhede et al 2020).…”

Small molecules in the treatment of COVID-19

“…Besides finding molecules with inhibitory effects on the S protein, studies focused on finding molecules which can inhibit the RBD–ACE2 interaction. 149 – 151 For example, Pei et al applied a computer-aided approach based on the RBD binding residues on ACE2 to design ultrashort peptide inhibitors against SARS-CoV-2. 152 Based on the critical residues of ACE2, they initially obtained the peptide inhibitor SI1.…”