Structural Bases of Coronavirus Attachment to Host Aminopeptidase N and Its Inhibition by Neutralizing Antibodies

• DOI: 10.1371/journal.ppat.1002859
• Publication Date: 2012-08-02T21:29:24Z
• Authors: Juan Reguera; César Santiago; Gaurav Mudgal; Desiderio Ordoño; Luis Enjuanes; José M. Casasnovas
• Keywords: Coronavirus

The coronaviruses (CoVs) are enveloped viruses of animals and humans associated mostly with enteric respiratory diseases, such as the severe acute syndrome 10–20% all common colds. A subset CoVs uses cell surface aminopeptidase N (APN), a membrane-bound metalloprotease, entry receptor. In these viruses, envelope spike glycoprotein (S) mediates attachment virus particles to APN subsequent entry, which can be blocked by neutralizing antibodies. Here we describe crystal structures receptor-binding domains (RBDs) two closely related CoV strains, transmissible gastroenteritis (TGEV) porcine (PRCV), in complex their receptor, (pAPN), or antibody. data provide detailed information on architecture dimeric pAPN ectodomain its interaction S. We show that protruding edge S determines virus-binding specificity for recessed glycan-containing surfaces membrane-distal region ectodomain. Comparison RBDs TGEV PRCV those other CoVs, suggests conformation receptor specificity. Moreover, is major antigenic determinant targeted Our results compelling view immune neutralization, may aid design antivirals vaccines. also considered target cancer therapy structure, reported here, could facilitate development anti-cancer drugs.