Identification of antiviral peptide inhibitors for receptor binding domain of SARS-CoV-2 omicron and its sub-variants: an in-silico approach

Abstract

Omicron, a variant of concern (VOC) of SARS-CoV-2, emerged in South Africa in November 2021. Omicron has been continuously acquiring a series of new mutations, especially in the spike (S) protein that led to high infectivity and transmissibility. Peptides targeting the receptor-binding domain (RBD) of the spike protein by which omicron and its variants attach to the host receptor, angiotensin-converting enzyme (ACE2) can block the viral infection at the first step. This study aims to identify antiviral peptides from the Antiviral peptide database (AVPdb) and HIV-inhibitory peptide database (HIPdb) against the RBD of omicron by using a molecular docking approach. The lead RBD binder peptides obtained through molecular docking were screened for allergenicity and physicochemical criteria (isoelectric point (pI) and net charge) required for peptide-based drugs. The binding affinity of the best five peptide inhibitors with the RBD of omicron was validated further by molecular dynamics (MD) simulation. Our result introduces five antiviral peptides, including AVP1056, AVP1059, AVP1225, AVP1801, and HIP755, that may effectively hinder omicron-host interactions. It is worth mentioning that all the three major sub-variants of omicron, BA.1 (B.1.1.529.1), BA.2 (B.1.1.529.2), and BA.3 (B.1.1.529.3), exhibits conserved ACE-2 interacting residues. Hence, the screened antiviral peptides with similar affinity can also interrupt the RBD-mediated invasion of different major sub-variants of omicron. Altogether, these peptides can be considered in the peptide-based therapeutics development for omicron treatment after further experimentation. Supplementary Information The online version contains supplementary material available at 10.1007/s13205-022-03258-4.

Identification of FDA-approved drugs with triple targeting mode of action for the treatment of monkeypox: a high throughput virtual screening study

“…The increase in SASA denotes that the ligand is unstable in the receptor’s binding pocket, exposing the binding site to the solvent molecules. In contrast, a decrease in SASA reflects that the ligand molecule alters the receptor so it can be compactly bound inside the binding site pocket and has less exposure to the solvent molecules [ 41 , 42 ]. The average value of SASA in the triplicate MD run for complex p37-Naldemedine, p37-Saquinavir, TK-Naldemedine, TK-Saquinavir, Topo-Naldemedine, and Topo-Saquinavir were calculated as 14708, 1478, 8151, 8244, 12220 and 12261 Å respectively.…”

An in‐silico‐based study identified peptide inhibitors that can block the egression of the monkeypox virus by inhibiting the p37 protein target

“…[ 75 ] According to current studies, a unique mutation in the viral genome is responsible for the MPV's rapid spread. [ 39 ] Furthermore, the virus might grow resistant to treatment and immunization because many possible targets have shown considerable mutation rates. [ 76 ] With the increasing knowledge of the benefits of peptides as therapeutics, [ 77 ] this study aimed to block the egression and spread of the MPXV by blocking the activity of the crucial peripheral membrane protein p37, essential for the successful propagation of the viral particle.…”

“…The computer‐aided peptide‐based drug has shown to be successful in different viral‐based diseases like HIV, covid‐19, and its variants. [ 39,77 ] However, our molecular docking study lacks experimental validation. We propose that further in vitro and in vivo studies may reveal the therapeutic potential of our peptide hits to block the monkeypox virus infection.…”

“…[38] The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), hydrogen bond interactions, Solvent Accessible Surface Area (SASA), and Radius of Gyration (Rg) were the parameters that were used to analyze the stability of the two complexes. [39,40] The output was visualized with the help of GraphPad Prism 9 software (https://www.graphpad.com/scientific-software/prism/).…”

In silico design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein

“…41 Recently, reports indicate that a phytochemical, curcumin, has been predicted to have some inhibitory potential against Omicron by computational methods. 42 Meanwhile, four medicinal compounds were screened from the South African Natural Compounds Database (SANCDB) 43 and five antiviral peptides were screened from the Antiviral peptide database (AVPdb) and HIV-inhibitory peptide database (HIPdb) 44 as potential antiviral agents against the Omicron variant by virtual drug screening and simulations. However, studies using point mutation and molecular dynamics (MD) simulations to screen high-affinity miniprotein inhibitors against the Omicron variant are limited.…”