A broad-spectrum macrocyclic peptide inhibitor of the SARS-CoV-2 spike protein.
Vito ThijssenDaniel L HurdissOliver J Debski-AntoniakMatthew A SpenceCharlotte FranckAlexander R NormanAnupriya AggarwalNadia J MokiemDavid A A van DongenStein W VermeirMinglong LiuWentao LiMarianthi ChatziandreouTim DonselaarWenjuan DuIeva DrulyteBerend-Jan BoschJoost SnijderStuart G TurvilleRichard J PayneColin J JacksonFrank J M van KuppeveldSeino A K JongkeesPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
The ongoing COVID-19 pandemic has had great societal and health consequences. Despite the availability of vaccines, infection rates remain high due to immune evasive Omicron sublineages. Broad-spectrum antivirals are needed to safeguard against emerging variants and future pandemics. We used messenger RNA (mRNA) display under a reprogrammed genetic code to find a spike-targeting macrocyclic peptide that inhibits SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Wuhan strain infection and pseudoviruses containing spike proteins of SARS-CoV-2 variants or related sarbecoviruses. Structural and bioinformatic analyses reveal a conserved binding pocket between the receptor-binding domain, N-terminal domain, and S2 region, distal to the angiotensin-converting enzyme 2 receptor-interaction site. Our data reveal a hitherto unexplored site of vulnerability in sarbecoviruses that peptides and potentially other drug-like molecules can target.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- binding protein
- angiotensin converting enzyme
- copy number
- genome wide
- coronavirus disease
- angiotensin ii
- healthcare
- single cell
- climate change
- mental health
- dna methylation
- electronic health record
- machine learning
- dna binding
- gene expression
- risk assessment
- artificial intelligence