美国得克萨斯大学奥斯汀分校Jason S. McLellan、比利时根特大学Xavier Saelens、Bert Schepens等研究人员合作解析了单域抗体高效中和β冠状病毒的结构基础。该项研究成果于2020年5月5日在线发表在《细胞》杂志上。
Title: Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies
Author: Daniel Wrapp, Dorien De Vlieger, Kizzmekia S. Corbett, Gretel M. Torres, Nianshuang Wang, Wander Van Breedam, Kenny Roose, Loes van Schie, Markus Hoffmann, Stefan Phlmann, Barney S. Graham, Nico Callewaert, Bert Schepens, Xavier Saelens, Jason S. McLellan
Issue&Volume: 2020-05-05
Abstract: Coronaviruses make use of a large envelope protein called spike (S) to engage host cell receptors and catalyze membrane fusion. Because of the vital role that these S proteins play, they represent a vulnerable target for the development of therapeutics. Here, we describe the isolation of single-domain antibodies (VHHs) from a llama immunized with prefusion-stabilized coronavirus spikes. These VHHs neutralize MERS-CoV or SARS-CoV-1 S pseudotyped viruses, respectively. Crystal structures of these VHHs bound to their respective viral targets reveal two distinct epitopes, but both VHHs interfere with receptor binding. We also show cross-reactivity between the SARS-CoV-1 S-directed VHH and SARS-CoV-2 S and demonstrate that this cross-reactive VHH neutralizes SARS-CoV-2 S pseudotyped viruses as a bivalent human IgG Fc-fusion. These data provide a molecular basis for the neutralization of pathogenic betacoronaviruses by VHHs and suggest that these molecules may serve as useful therapeutics during coronavirus outbreaks.
DOI: 10.1016/j.cell.2020.04.031
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30494-3