Dataset Information

In-Silico Design of a Novel Tridecapeptide Targeting Spike Protein of SARS-CoV-2 Variants of Concern.

ABSTRACT: Several mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased the transmission and mortality rate of coronavirus disease-19 (COVID-19) across the globe. Although many vaccines have been developed, a large proportion of the global population remains at high risk of infection. The current study aims to develop an antiviral peptide capable of inhibiting the interaction of SARS-CoV-2 spike protein and its six major variants with the host cell angiotensin-converting enzyme 2 (ACE2) receptor. An in-silico approach was employed to design a therapeutic peptide inhibitor against the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 and its variants (B.1.1.7, B.1.351, P.1, B.1.617.1, B.1.617.2 and B.1.617.3). The binding specificity and affinity of our designed peptide inhibitor Mod13AApi (YADKYQKQYKDAY) with wild-type S-RBD and its six variants was confirmed by molecular docking using the HPEPDOCK tool, whereas complex stability was determined by the MD simulation study. The physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of inhibitory peptides were determined using the ExPASy tool and pkCSM server. The docking results and its properties from our in-silico analysis present the Mod13AApi, a promising peptide for the rapid development of anti-coronavirus peptide-based antiviral therapy. Blockage of the binding of the spike protein of SARS-CoV-2 variants with ACE2 in the presence of the therapeutic peptide may prevent deadly SARS-CoV-2 variants entry into host cells. Therefore, the designed inhibitory peptide can be utilized as a promising therapeutic strategy to combat COVID-19, as evident from this in-silico study.

SUBMITTER: Rajpoot S

PROVIDER: S-EPMC8667532 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Since first reported in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly acquiring mutations, particularly in the spike protein, that can modulate pathogenicity, transmission and antibody evasion leading to successive waves of COVID19 infections despite an unprecedented mass vaccination necessitating continuous adaptation of therapeutics. Small animal models can facilitate understanding host-pathogen interactions, target selection for therapeutic drugs, and vaccine development, but availability and cost of studies in BSL3 facilities hinder progress. To generate a BSL2-compatible in vivo system that specifically recapitulates spike protein mediated disease we used replication competent, GFP tagged, recombinant Vesicular Stomatitis Virus where the VSV glycoprotein was replaced by the SARS-CoV-2 spike protein (rVSV-SARS2-S). We show that infection requires hACE2 and challenge of neonatal but not adult, K18-hACE2 transgenic mice (hACE2tg) leads to productive infection of the lungs and brains. Although disease progression was faster in SARS-CoV-2 infected mice, infection with both viruses resulted in neuronal infection and encephalitis with increased expression of Interferon-stimulated Irf7, Bst2, Ifi294, as well as CxCL10, CCL5, CLC2, and LILRB4, and both models were uniformly lethal. Further, prophylactic treatment targeting the Spike protein (Receptor Binding Domain) with antibodies resulted in similar levels of protection from lethal infection against rVSV-SARS2-S and SARS-CoV-2 viruses. Strikingly, challenge of neonatal hACE2tg mice with SARS-CoV-2 Variants of Concern (SARS-CoV-2-α, -β, ϒ, or Δ) or the corresponding rVSV-SARS2-S viruses (rVSV-SARS2-Spike-α, rVSV-SARS2-Spike-β, rVSV-SARS2-Spike-ϒ or rVSV-SARS2-Spike-Δ) resulted in increased lethality, suggesting that the Spike protein plays a key role in determining the virulence of each variant. Thus, we propose that rVSV-SARS2-S virus can be used to understand the effect of changes to SARS-CoV-2 spike protein on infection and to evaluate existing or experimental therapeutics targeting spike protein of current or future VOC of SARS-CoV-2 under BSL-2 conditions.

Dataset Information

In-Silico Design of a Novel Tridecapeptide Targeting Spike Protein of SARS-CoV-2 Variants of Concern.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets