Targeting ACE2 with a camelid antibody inhibits SARS-CoV-2 binding and has protective effects in vivo.

ABSTRACT: The continuous emergence of antibody-escape variants of SARS-CoV-2 demands the identification of alternative methods of protection against infection that do not directly target viral proteins. Here, we generated heavy-chain-only antibody (VHHs) from an alpaca immunized with the human angiotensin-converting enzyme 2 (hACE2), the major entry receptor for SARS-CoV-2. The VHHs bind hACE2 without affecting its enzymatic activity, and two of them (B07 and B09) inhibit all SARS-CoV-2 isolates tested (Delta, BA.1, BQ1.1, XBB.1.5, XBB.1.16.1, EG.5.1.3, BA.2.86.1). Their X-ray structure in complex with hACE2 show that their epitope overlaps with the footprint of the receptor binding domain (RBD) of the SARS-CoV-2 spike on hACE2. A dimeric B07-Fc fusion construct avidly binds hACE2 with an apparent d

SUBMITTER: Blachier S 

PROVIDER: S-EPMC12638815 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature