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.
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.
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…