Different SARS-CoV-2 variants inhibited by RRM designed peptide

Abstract

The SARS-CoV-2 virus has mutated over time, resulting in variations of circulating viral variants, which may impact the virus's properties, such as transmission or the severity of symptoms. Thus, there is a need for comprehensive approach less dependent of viral variants. For that purpose, we have employed the innovative and unique Resonant Recognition Model (RRM) to identify the common characteristics of all variants of SARS-CoV-2 virus and based on these characteristics, we have explored the possibility to develop approach against SARS-CoV-2 infection, less dependent on viral variants. This paper is a continuation of our previous research, where we have used the RRM model to design de novo peptide CovA, capable to prevent SARS-CoV-2 interaction with ACE2 receptor on host cells. Using Inhibitor Screening Assay Kits and viral replication in SARS-CoV-2/Vero E6 cells model, it has been previously shown that CovA can prevent viral interaction with receptor and viral replication in host cells. This test has been done on Wuhan variant only. Here, we have tested this RRM designed peptide CovA for efficiency with some other different SARS-CoV-2 variants. It has been shown here, that CovA act on all tested viral variants, but with different efficiency. Apart from representing the basis of new COVID-19 drugs discovery, this research once again presents the ability of RRM model to design de novo bioactive peptides with desired biological function.

Fig 1. RRM parameters for different SARS-CoV-2 variants.

S/N ratio at RRM characteristic frequency f1 in blue for whole spike protein and frequency f2 in orange for S1 spike fragment for different SARS-CoV-2 variants. It can be observed that more virulent variants have higher S/N ratio at RRM characteristic frequencies f2 (orange bars) and that strength of virus variant is correlated with S/N ratio at RRM characteristic frequencies f1 (blue bars) [–20].

Fig 2. Ct values forviral RNA for different SARS-CoV-2 variants.

Ct values (PCR threshold cycles) are presented for viral RNA in orange and GAPDH in blue as control for variants: a) Alpha, b) Delta c) Wuhan and d) Omicron. It can be observed that RRM designed peptide CovA prevent Alpha, Delta, Wuhan and Omicron infection and replication in the Vero E6 cell culture model, but with different efficiency.

Fig 3. RT-qPCR determination of viral RNA for different SARS-CoV-2 variants.

Viral RNA was determined with RT-qPCR targeting the E gene of SARS-CoV-2, using GAPDH as a control. Results are presented as fold change compared to non-treated cells after normalisation to GAPDH expression analysed. The Y axis on the right side represent intracellular RNA quantities in percentages of control. Peptide CovA inhibits viral entry and replication of Alpha, Delta, Wuhan and Omicron SARS-CoV-2 variants, but with different efficiency. The inhibitory activity of the peptide CovA was tested eight times at the indicated concentrations.