Spike residue 403 affects binding of coronavirus spikes to human ACE2.
Fabian ZechDaniel SchniertshauerChristoph JungAlexandra HerrmannArne CordsmeierQinya XieRayhane NchiouaCaterina Prelli BozzoMeta VolcicLennart KoepkeJanis A MüllerJana KrügerSandra HellerSteffen StengerMarkus HoffmannStefan H PöhlmannAlexander KlegerTimo JacobKarl Klaus ConzelmannArmin EnsserKonstantin Maria Johannes SparrerFrank KirchhoffPublished in: Nature communications (2021)
The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, the cause of the COVID-19 pandemic. However, this bat virus was most likely unable to directly infect humans since its Spike (S) protein does not interact efficiently with the human ACE2 receptor. Here, we show that a single T403R mutation increases binding of RaTG13 S to human ACE2 and allows VSV pseudoparticle infection of human lung cells and intestinal organoids. Conversely, mutation of R403T in the SARS-CoV-2 S reduces pseudoparticle infection and viral replication. The T403R RaTG13 S is neutralized by sera from individuals vaccinated against COVID-19 indicating that vaccination might protect against future zoonoses. Our data suggest that a positively charged amino acid at position 403 in the S protein is critical for efficient utilization of human ACE2 by S proteins of bat coronaviruses. This finding could help to better predict the zoonotic potential of animal coronaviruses.
Keyphrases
- sars cov
- endothelial cells
- amino acid
- induced pluripotent stem cells
- respiratory syndrome coronavirus
- angiotensin ii
- pluripotent stem cells
- angiotensin converting enzyme
- binding protein
- coronavirus disease
- artificial intelligence
- machine learning
- climate change
- risk assessment
- small molecule
- signaling pathway
- protein protein
- dna binding
- cell proliferation
- human health
- endoplasmic reticulum stress