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. The bat sarbecovirus RaTG13 is a close relative of SARS-CoV-2, but its spike protein doesn’t efficiently bind human ACE2. Here, the authors show that exchange of spike residue 403 between RaTG13 and SARS-CoV-2 spike proteins affects binding to human ACE2 and entry of pseudotyped viruses.
【저자키워드】 Microbiology, Molecular biology, 【초록키워드】 zoonoses, SARS-CoV-2, vaccination, Mutation, S protein, spike, COVID-19 pandemic, Human, Infection, virus, Spike protein, human ACE2, Protein, VSV, viral replication, sera, zoonotic, SARS-CoV-2 spike protein, RaTG13, Pseudotyped viruses, Critical, predict, binding, sarbecovirus, Amino acid, bat coronaviruses, Animal coronaviruses, Intestinal Organoids, individual, residue, help, human ACE2 receptor, infect, Affect, neutralized, PROTECT, increase, the S protein, reduce, human lung cell, the SARS-CoV-2, vaccinated against COVID-19, 【제목키워드】 coronavirus, spike, human ACE2, binding, residue, Affect,