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Structure paper

TitleCharacterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75.
Journal, issue, pagesCell Host Microbe, Vol. 30, Issue 11, Page 1527-11539.e5, Year 2022
Publish dateNov 9, 2022
AuthorsYunlong Cao / Weiliang Song / Lei Wang / Pan Liu / Can Yue / Fanchong Jian / Yuanling Yu / Ayijiang Yisimayi / Peng Wang / Yao Wang / Qianhui Zhu / Jie Deng / Wangjun Fu / Lingling Yu / Na Zhang / Jing Wang / Tianhe Xiao / Ran An / Jing Wang / Lu Liu / Sijie Yang / Xiao Niu / Qingqing Gu / Fei Shao / Xiaohua Hao / Bo Meng / Ravindra Kumar Gupta / Ronghua Jin / Youchun Wang / Xiaoliang Sunney Xie / Xiangxi Wang /
PubMed AbstractRecently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced ...Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations.
External linksCell Host Microbe / PubMed:36270286 / PubMed Central
MethodsEM (single particle)
Resolution3.19 - 3.98 Å
Structure data

34034

7yqt

EMDB-34034, PDB-7yqt:
SARS-CoV-2 BA.2.75 S Trimer (1 RBD Up)
Method: EM (single particle) / Resolution: 3.45 Å

34035

7yqu

EMDB-34035, PDB-7yqu:
SARS-CoV-2 BA.2.75 S Trimer (3 RBD Down)
Method: EM (single particle) / Resolution: 3.19 Å

34036

7yqv

EMDB-34036, PDB-7yqv:
pH 5.5 SARS-CoV-2 BA.2.75 S Trimer (1 RBD Up)
Method: EM (single particle) / Resolution: 3.58 Å

34037

7yqw

EMDB-34037, PDB-7yqw:
SARS-CoV-2 BA.2.75 S Trimer (3 RBD Down)
Method: EM (single particle) / Resolution: 3.51 Å

34038

7yqx

EMDB-34038, PDB-7yqx:
SARS-CoV-2 BA.2.75 S Trimer in complex with S309 (state1)
Method: EM (single particle) / Resolution: 3.72 Å

34039

7yqy

EMDB-34039, PDB-7yqy:
SARS-CoV-2 BA.2.75 S Trimer in complex with S309 (state2)
Method: EM (single particle) / Resolution: 3.74 Å

34040

7yqz

EMDB-34040, PDB-7yqz:
SARS-CoV-2 BA.2.75 S Trimer in complex with S309 (state3)
Method: EM (single particle) / Resolution: 3.84 Å

34041

7yr0

EMDB-34041, PDB-7yr0:
SARS-CoV-2 BA.2.75 S Trimer in complex with S309 (interface)
Method: EM (single particle) / Resolution: 3.98 Å

34042

7yr1

EMDB-34042, PDB-7yr1:
SARS-CoV-2 BA.2.75 S Trimer in complex with XG2v024
Method: EM (single particle) / Resolution: 3.62 Å

34043

7yr2

EMDB-34043, PDB-7yr2:
SARS-CoV-2 BA.2.75 S Trimer in complex with ACE2(state1)
Method: EM (single particle) / Resolution: 3.3 Å

34044

7yr3

EMDB-34044, PDB-7yr3:
SARS-CoV-2 BA.2.75 S Trimer in complex with ACE2(state2)
Method: EM (single particle) / Resolution: 3.52 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-ZN:
Unknown entry

ChemComp-CL:
Unknown entry / Chloride

ChemComp-HOH:
WATER / Water

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / spike / STRUCTURAL PROTEIN / SARS-CoV-2 / BA.2.75 / pH5.5 / S309 / VIRALPROTEIN

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