Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association

• DOI: 10.1073/pnas.0307140101
• Publication Date: 2004-02-25T04:03:03Z
• Authors: Jianhua Sui; Wenhui Li; Akikazu Murakami; Azaibi Tamin; Leslie J. Matthews; Swee Kee Wong; Michael J. Moore; Aimee St. Clair T...; Mobolaji Olurinde; Hyeryun Choe; Larry J. Anderson; William J. Bellini; Michael Farzan; Wayne A. Marasco
• Keywords: Coronavirus; Epitope mapping; Nidovirales

Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence highly contagious often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against S1 domain spike (S) protein SARS-CoV from two nonimmune antibody libraries. One scFv 80R efficiently neutralized inhibited syncytia formation between cells expressing S those receptor angiotensin-converting enzyme 2 (ACE2). Mapping epitope showed it is located within N-terminal 261–672 amino acids not glycosylation-dependent. competed with soluble ACE2 for association bound high affinity (equilibrium dissociation constant, K d = 32.3 nM). A IgG1 form a 20-fold higher 1.59 nM comparable to that ( 1.70 nM), virus more than scFv. These data suggest monoclonal may be useful viral entry inhibitor emergency treatment SARS, ACE2-binding site could an attractive target subunit vaccine drug development.