Your browser doesn't support javascript.
Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies.
Li, Ruofan; Mor, Michael; Ma, Bingting; Clark, Alex E; Alter, Joel; Werbner, Michal; Lee, Jamie Casey; Leibel, Sandra L; Carlin, Aaron F; Dessau, Moshe; Gal-Tanamy, Meital; Croker, Ben A; Xiang, Ye; Freund, Natalia T.
  • Li R; Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Mor M; Department for Microbiology and Clinical Immunology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Ma B; Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China.
  • Clark AE; Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • Alter J; The Laboratory of Structural Biology of Infectious Diseases, Azrieli Faculty of Medicine, Bar Ilan University, Tsafed, Israel.
  • Werbner M; Molecular Virology Lab, Azrieli Faculty of Medicine, Bar Ilan University, Tsafed, Israel.
  • Lee JC; Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA, USA.
  • Leibel SL; Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA, USA.
  • Carlin AF; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
  • Dessau M; Department of Medicine, University of California San Diego, La Jolla, CA, USA.
  • Gal-Tanamy M; The Laboratory of Structural Biology of Infectious Diseases, Azrieli Faculty of Medicine, Bar Ilan University, Tsafed, Israel.
  • Croker BA; Molecular Virology Lab, Azrieli Faculty of Medicine, Bar Ilan University, Tsafed, Israel.
  • Xiang Y; Department of Pediatrics, School of Medicine, UC San Diego, La Jolla, CA, USA. bcroker@health.ucsd.edu.
  • Freund NT; Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, China. yxiang@mail.tsinghua.edu.cn.
Commun Biol ; 5(1): 789, 2022 08 05.
Article in English | MEDLINE | ID: covidwho-2117221
ABSTRACT
As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection. In the present study, we evaluate the activity of nine anti-SARS-CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviruses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which retain their potency against all VOCs tested. At the second part of our study, we reveal the neutralization mechanisms at high molecular resolution of two anti-SARS-CoV-2 neutralizing mAbs by structural characterization. We solve the structures of the Delta-neutralizing ACE2bs mAb TAU-2303 with the SARS-CoV-2 spike trimer and RBD at 4.5 Å and 2.42 Å resolutions, respectively, revealing a similar mode of binding to that between the RBD and ACE2. Furthermore, we provide five additional structures (at resolutions of 4.7 Å, 7.3 Å, 6.4 Å, 3.3 Å, and 6.1 Å) of a second antibody, TAU-2212, complexed with the SARS-CoV-2 spike trimer. TAU-2212 binds an exclusively quaternary epitope, and exhibits a unique, flexible mode of neutralization that involves transitioning between five different conformations, with both arms of the antibody recruited for cross linking intra- and inter-spike RBD subunits. Our study provides additional mechanistic understanding about how antibodies neutralize SARS-CoV-2 and its emerging variants and provides insights on the likelihood of reinfections.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03739-5

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Randomized controlled trials Topics: Variants Limits: Humans Language: English Journal: Commun Biol Year: 2022 Document Type: Article Affiliation country: S42003-022-03739-5