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A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates.


ABSTRACT: The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SARS-CoV-2 variants. Furthermore, 6D6 effectively protected hamster from the virulent Beta strain. Sequence alignment of approximately 6 million documented SARS-CoV-2 isolates revealed that 6D6 epitope maintains an exceptionally high conservation rate (99.92%). Structural analysis demonstrated that all 33 mutations accumulated in XBB.1.5 since the original strain do not perturb the binding 6D6 to RBD, in line with the sequence analysis throughout the antigenicity evolution of SARS-CoV-2. These findings suggest the potential of this epitope serving as a critical determinant for vaccines and therapeutic design.

SUBMITTER: Cui L 

PROVIDER: S-EPMC11251093 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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A cryptic site in class 5 epitope of SARS-CoV-2 RBD maintains highly conservation across natural isolates.

Cui Lingyan L   Li Tingting T   Lan Miaolin M   Zhou Ming M   Xue Wenhui W   Zhang Sibo S   Wang Hong H   Hong Minqing M   Zhang Yali Y   Yuan Lunzhi L   Sun Hui H   Ye Jianghui J   Zheng Qingbing Q   Guan Yi Y   Gu Ying Y   Xia Ningshao N   Li Shaowei S  

iScience 20240611 7


The emergence of SARS-CoV-2 variants raises concerns about the efficacy of existing COVID-19 vaccines and therapeutics. Previously, we identified a conserved cryptic class 5 epitope of SARS-CoV-2 receptor binding domain (RBD) by two cross-neutralizing antibodies 7D6 and 6D6. Intriguingly, this site remains resistant to substantial mutations occurred in ever-changing SARS-CoV-2 subvariants. As compared to class 3 antibody S309, 6D6 maintains broad and consistent neutralizing activities against SA  ...[more]

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