Identifying epitopes for cluster of differentiation and design of new peptides inhibitors against human SARS-CoV-2 spike RBD by an in-silico approach

Abstract

The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some cases, the disease can be fatal which resulted in more than one million deaths worldwide according the WHO. Currently, there is no effective vaccine or treatment for COVID-19, however many small-molecule inhibitors have shown potent antiviral activity against SARS-CoV-2 and some of them are now under clinical trials. Despite their promising activities, the development of these small molecules for the clinical use can be limited by many factors like the off-target effect, the poor stability, and the low bioavailability. The clusters of differentiation CD147, CD209, CD299 have been identified as essential entry co-receptors for SARS-CoV-2 species specificity to humans, although the underlying mechanisms are yet to be fully elucidated. In this paper, protein-protein docking was utilized for identifying the critical epitopes in CD147, CD209 and CD299 which are involved in the binding with SARS-CoV-2 Spike receptor binding domain (RBD). The results of binding free energies showed a high affinity of SARS-CoV-2 RBD to CD299 receptor which was used as a reference to derive hypothetical peptide sequences with specific binding activities to SARS-CoV-2 RBD. Molecular docking and molecular dynamics simulations of the newly designed peptides showed favorable binding features and stability with SARS-CoV-2 RBD and therefore can be further considered as potential candidates in future anti-SARS CoV-2 drug discovery studies.

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

“…In silico computational approaches have been utilized in this regard as the first step to screen potential inhibitors such as small organic molecules, natural products, peptide mimics or miniproteins to block spike-ACE2 intermolecular interactions (Prashantha et al 2021;Ribaudo et al 2021;Schütz et al 2020). Published PDB crystal structures were then extensively used by previous investigators to study and analyze spike S-glycoprotein and ACE2 receptor interactions (Day et al 2021;Akachar et al 2020).…”

Comparative genomics, evolutionary epidemiology, and RBD-hACE2 receptor binding pattern in B.1.1.7 (Alpha) and B.1.617.2 (Delta) related to their pandemic response in UK and India

“…Several scientists have used the HawkDock server to calculate BFE. Akachar et al have used the HawkDock server to understand the binding efficiency of newly designed peptides inhibitors against spike RBD SARS-CoV-2 ( Akachar et al, 2020 ). Parate et al (2021) have applied the HawkDock server to illustrate the BFE of the binding interaction of the inhibitory protein of Raf Kinase ( Parate et al, 2021 ).…”

Protein interactions with metallothionein-3 promote vectorial active transport in human proximal tubular cells

“…Simulation of K d and ΔG weigh intermolecular attractive forces to a greater extent than Docking Score and MMGBSA, which place more emphasis on complementary fit and surface topology [ 71 ]. An analysis of SARS-CoV-2 spike protein variants in its interaction with ACE2 receptor is another example where each in silico approach gave different binding rankings for each in silico approach [ 72 ].…”