Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants

Yang，Haonan1; Guo，Huimin2; Wang，Aojie1,3; Cao，Liwei1; Fan，Qing2; Jiang，Jie2; Wang，Miao2; Lin，Lin4; Ge，Xiangyang2; Wang，Haiyan2; Zhang，Runze1; Liao，Ming5,6; Yan，Renhong1; Ju，Bin2,7; Zhang，Zheng2,7,8

2024-12-01

10.1038/s41467-024-51973-8

Nature Communications   影响因子和分区

2041-1723

The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

英语

第一 ; 通讯

2-s2.0-85203176209

Scopus

1.Department of Biochemistry,Key University Laboratory of Metabolism and Health of Guangdong,School of Medicine,Institute for Biological Electron Microscopy,Southern University of Science and Technology,Shenzhen,Guangdong Province,China
2.Institute for Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital; The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong Province,China
3.Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control,College of Veterinary Medicine,South China Agricultural University,Guangzhou,Guangdong Province,China
4.Sustech Core Research Facilities,Southern University of Science and Technology,Shenzhen,Guangdong Province,China
5.College of Animal Science & amp; Technology,Zhong Kai University of Agriculture and Engineering,Guangzhou,Guangdong Province,China
6.Key Laboratory of Livestock Disease Prevention of Guangdong Province,Institute of Animal Health,Guangdong Academy of Agricultural Sciences,Guangzhou,Guangdong Province,China
7.Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation,Shenzhen,Guangdong Province,China
8.Shenzhen Research Center for Communicable Disease Diagnosis and Treatment,Chinese Academy of Medical Sciences,Shenzhen,Guangdong Province,China

Yang，Haonan,Guo，Huimin,Wang，Aojie,et al. Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants[J]. Nature Communications,2024,15(1).

Yang，Haonan.,Guo，Huimin.,Wang，Aojie.,Cao，Liwei.,Fan，Qing.,...&Zhang，Zheng.(2024).Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants.Nature Communications,15(1).

Yang，Haonan,et al."Structural basis for the evolution and antibody evasion of SARS-CoV-2 BA.2.86 and JN.1 subvariants".Nature Communications 15.1(2024).