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Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms #MMPMID32972994
Tortorici MA; Beltramello M; Lempp FA; Pinto D; Dang HV; Rosen LE; McCallum M; Bowen J; Minola A; Jaconi S; Zatta F; De Marco A; Guarino B; Bianchi S; Lauron EJ; Tucker H; Zhou J; Peter A; Havenar-Daughton C; Wojcechowskyj JA; Case JB; Chen RE; Kaiser H; Montiel-Ruiz M; Meury M; Czudnochowski N; Spreafico R; Dillen J; Ng C; Sprugasci N; Culap K; Benigni F; Abdelnabi R; Foo SC; Schmid MA; Cameroni E; Riva A; Gabrieli A; Galli M; Pizzuto MS; Neyts J; Diamond MS; Virgin HW; Snell G; Corti D; Fink K; Veesler D
Science 2020[Nov]; 370 (6519): 950-957 PMID32972994show ga
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.