4.7 Article

Biosynthetic proteins targeting the SARS-CoV-2 spike as anti-virals

Journal

PLOS PATHOGENS
Volume 18, Issue 9, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1010799

Keywords

-

Funding

  1. Agence Nationale de la Recherche (ANR)
  2. Federation pour la recherche medicale (ANR 20 Flash Covid 19 -FRM program)

Ask authors/readers for more resources

The study identified candidates that can interact with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, inhibiting virus entry into cells and neutralizing various SARS-CoV-2 variants. These findings provide a new strategy for developing therapeutics against SARS-CoV-2.
The binding of the SARS-CoV-2 spike to angiotensin-converting enzyme 2 (ACE2) promotes virus entry into the cell. Targeting this interaction represents a promising strategy to generate antivirals. By screening a phage-display library of biosynthetic protein sequences build on a rigid alpha-helicoidal HEAT-like scaffold (named aReps), we selected candidates recognizing the spike receptor binding domain (RBD). Two of them (F9 and C2) bind the RBD with affinities in the nM range, displaying neutralisation activity in vitro and recognizing distinct sites, F9 overlapping the ACE2 binding motif. The F9-C2 fusion protein and a trivalent alpha Rep form (C2-foldon) display 0.1 nM affinities and EC50 of 8-18 nM for neutralization of SARS-CoV-2. In hamsters, F9-C2 instillation in the nasal cavity before or during infections effectively reduced the replication of a SARS-CoV-2 strain harbouring the D614G mutation in the nasal epithelium. Furthermore, F9-C2 and/or C2-foldon effectively neutralized SARS-CoV-2 variants (including delta and omicron variants) with EC50 values ranging from 13 to 32 nM. With their high stability and their high potency against SARS-CoV-2 variants, alpha Reps provide a promising tool for SARS-CoV-2 therapeutics to target the nasal cavity and mitigate virus dissemination in the proximal environment.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available