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A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection

By Hejun Liu, Meng Yuan, Deli Huang, Sandhya Bangaru, Chang-Chun D. Lee, Linghang Peng, Xueyong Zhu, David Nemazee, Marit J. van Gils, Rogier W Sanders, Hans-Christian Kornau, S Momsen Reincke, Harald Pruess, Jakob Kreye, Nicholas C. Wu, Andrew B. Ward, Ian A. Wilson

Posted 12 Feb 2021
bioRxiv DOI: 10.1101/2021.02.11.430866

Coronaviruses have caused several epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Some prophylactic vaccines and therapeutic antibodies have already showed striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well as threats from other sarbecoviruses. Cross-neutralizing antibodies to SARS-related viruses provide opportunities to address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody CV38-142 in complex with the receptor binding domains from SARS-CoV-2 and SARS-CoV. Our structural findings provide mechanistic insights into how this antibody can accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, in particular COVA1-16, to enhance neutralization of SARS-CoV-2 and SARS-CoV. Overall, this study provides valuable information for vaccine and therapeutic design to address current and future antigenic drift in SARS-CoV-2 and to protect against zoonotic coronaviruses.

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