Researchers in the United States have developed an inhibitor of the spike protein found on the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that limits its formation in host human cells that would otherwise be the source of newly generated virions.
The SARS-CoV-2 virus is the agent responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic and the spike protein is the main structure the virus relies on for host cell entry.
Importantly, the inhibitor was effective against the spike proteins of other coronaviruses, including SARS-CoV-1 and Middle East respiratory syndrome CoV (MERS-CoV).
Furthermore, the researchers say the polypeptide inhibitor – called F1 – is expected to be effective against the spike proteins of almost any SARS-CoV-2 variants that may emerge in the future.
“We expect the inhibitor reported here to be an invaluable aid to help end the COVID-19 pandemic,” writes Jianpeng Ma and colleagues from Baylor College of Medicine in Houston, Texas.
A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.
.jpg "Study: High-Potency Polypeptide-based Interference for Coronavirus Spike Glycoproteins. Image Credit: NIAID")
Study: High-Potency Polypeptide-based Interference for Coronavirus Spike Glycoproteins. Image Credit: NIAID
Coronaviruses have posed a major threat for two decades
Within just the last 20 years, three coronaviruses have posed a significant threat to public health, causing regional and global outbreaks of potentially life-threatening respiratory disease.
These include the SARS-CoV-1 virus responsible for the 2002 to 2003 SARS outbreak, the MERS-CoV virus that has caused various outbreaks across the Middle East since 2012, and the novel SARS-CoV-2 virus that is responsible for the ongoing COVID-19 pandemic.
Currently, researchers are racing to develop vaccines based on the SARS-CoV-2 spike protein that will generate immune responses against the wild-type spike following natural infection with the virus.
The concept of polypeptide-based protein interference against coronavirus spike proteins. a). Domain organization of COVID-19 SARS2-S, the mutations in recent variants and the design of interfering polypeptides F1 and F2. SP: Signal peptide; NTD: N-terminal domain; RBD: receptor-binding domain; SD1: subdomain 1; SD2: subdomain 2; FP: fusion peptide; HR1: heptad repeat 1; HR2: heptad repeat 2; TM: transmembrane domain; CT: Cytoplasmic tail. The cleavage at S1/S2 (red arrow) gives rise to N-terminal S1 fragment and C-terminal S2 fragment. The signal peptide sequence at the extreme N-termini of F1 and F2 allowed the polypeptides to be translocated in the same way as COVID-19 SARS2-S. At the extreme C-termini, SARS2-S had a C9 epitope recognized by C9-rhodopsin antibody 1D4, while both F1 and F2 had a FLAG-tag. b). Diagram of polypeptide-based interference targeting coronavirus spike proteins. Top row: in the normal situation, the spike proteins were synthesized, folded and formed native spike oligomers, which were anchored on virion envelope. Bottom row, interfering polypeptides formed nonnative oligomers with the wild-type spike proteins, thus reducing the level of native spike oligomers on the envelope of…
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