Breadth of ACE2 receptor usage predicts host range and antigenic relatedness across bat sarbecoviruses

The useful part

Doores, Dalan Bailey Sarbecoviruses interact with their receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of Spike, the immunodominant target for neutralising antibodies. vitally important for understanding the zoonotic potential of related bat sarbecoviruses. Using binding assays, pseudotype-entry assays and a diverse panel of mammalian ACE2 proteins, we examined the host range and related antigenicity of multiple bat coronaviruses.

How it works

• clade 3 (e.g., RhGB07) and 5 (e.g., Rc-o319) sarbecoviruses exhibited more restricted ACE2 usage (a specialist phenotype).
• A novel structure for RhGB07 Spike further helped to identify RBD residues associated with this receptor specialism.
• The impact of SARS-CoV-2's continued evolution in humans was also examined, identifying an expanding and/or shifting pattern of generalism for variants, especially Omicron and its sub-lineages.

Details worth keeping

by Nazia Thakur, Joseph Newman, Dongchun Ni, Jeffrey Seow, Abigail L. Hay, Yeonjae Lee, Ayush Upadhyay, Babatunde E. Interestingly, the generalist phenotypes were largely maintained with more diverse mammalian receptor libraries, including human, non-human primate, livestock, rodent ACE2 and potential intermediate reservoir hosts (e.g., civet, racoon dog, pangolin), while specialists, like RhGB07, exhibited wider phenotypic diversity.