tetano
Editor, Senior Moderator
Cell Host Microbe
. 2021 Apr 15;S1931-3128(21)00181-5.
doi: 10.1016/j.chom.2021.04.005. Online ahead of print.
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection
Hejun Liu[SUP] 1 [/SUP], Meng Yuan[SUP] 1 [/SUP], Deli Huang[SUP] 2 [/SUP], Sandhya Bangaru[SUP] 1 [/SUP], Fangzhu Zhao[SUP] 2 [/SUP], Chang-Chun D Lee[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Shawn Barman[SUP] 2 [/SUP], Xueyong Zhu[SUP] 1 [/SUP], David Nemazee[SUP] 2 [/SUP], Dennis R Burton[SUP] 3 [/SUP], Marit J van Gils[SUP] 4 [/SUP], Rogier W Sanders[SUP] 5 [/SUP], Hans-Christian Kornau[SUP] 6 [/SUP], S Momsen Reincke[SUP] 7 [/SUP], Harald Pr?ss[SUP] 7 [/SUP], Jakob Kreye[SUP] 8 [/SUP], Nicholas C Wu[SUP] 9 [/SUP], Andrew B Ward[SUP] 1 [/SUP], Ian A Wilson[SUP] 10 [/SUP]
Affiliations
Abstract
Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown 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. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. 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 SARS-related coronaviruses.
Keywords: 3D structure; COVID-19; SARS-CoV-2; antibody cocktail; antibody-antigen interaction; coronavirus; cross-neutralizing antibody; crystallography; synergy.
. 2021 Apr 15;S1931-3128(21)00181-5.
doi: 10.1016/j.chom.2021.04.005. Online ahead of print.
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection
Hejun Liu[SUP] 1 [/SUP], Meng Yuan[SUP] 1 [/SUP], Deli Huang[SUP] 2 [/SUP], Sandhya Bangaru[SUP] 1 [/SUP], Fangzhu Zhao[SUP] 2 [/SUP], Chang-Chun D Lee[SUP] 1 [/SUP], Linghang Peng[SUP] 2 [/SUP], Shawn Barman[SUP] 2 [/SUP], Xueyong Zhu[SUP] 1 [/SUP], David Nemazee[SUP] 2 [/SUP], Dennis R Burton[SUP] 3 [/SUP], Marit J van Gils[SUP] 4 [/SUP], Rogier W Sanders[SUP] 5 [/SUP], Hans-Christian Kornau[SUP] 6 [/SUP], S Momsen Reincke[SUP] 7 [/SUP], Harald Pr?ss[SUP] 7 [/SUP], Jakob Kreye[SUP] 8 [/SUP], Nicholas C Wu[SUP] 9 [/SUP], Andrew B Ward[SUP] 1 [/SUP], Ian A Wilson[SUP] 10 [/SUP]
Affiliations
- PMID: 33894127
- DOI: 10.1016/j.chom.2021.04.005
Abstract
Coronaviruses have caused several human epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Prophylactic vaccines and therapeutic antibodies have already shown 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. Recognition of the N343 glycosylation site and water-mediated interactions facilitate cross-reactivity of CV38-142 to SARS-related viruses, allowing the antibody to accommodate antigenic variation in these viruses. CV38-142 synergizes with other cross-neutralizing antibodies, notably COVA1-16, to enhance neutralization of SARS-CoV and SARS-CoV-2, including circulating variants of concern B.1.1.7 and B.1.351. 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 SARS-related coronaviruses.
Keywords: 3D structure; COVID-19; SARS-CoV-2; antibody cocktail; antibody-antigen interaction; coronavirus; cross-neutralizing antibody; crystallography; synergy.