期刊
JOURNAL OF MEDICAL VIROLOGY
卷 94, 期 5, 页码 2019-2025出版社
WILEY
DOI: 10.1002/jmv.27577
关键词
antibody susceptibility; coronavirus; evolution; infection; pathogenesis; SARS coronavirus; virulence; virus classification
类别
资金
- French Government under the Investments for the Future program [MediterraneeInfection 10-IAHU-03]
- Region Provence Alpes Cote d'Azur
- European funding FEDER PRIMMI (Fonds Europeen de Developpement RegionalPlateformes de Recherche et d'Innovation Mutualisees Mediterranee Infection) [FEDER PA 0000320 PRIMMI]
- Hitachi High-Technologies Corporation, Tokyo, Japan
The recently emerging SARS-CoV-2 variant omicron has a unique set of mutations and exhibits decreased affinity for the ACE-2 receptor compared to the delta variant. The omicron variant is predicted to be less pathogenic but may evade neutralizing antibodies generated by current vaccines, suggesting a potential decrease in vaccine effectiveness.
The recently emerging SARS-CoV-2 variant omicron displays an unusual association of 30 mutations, 3 deletions, and 1 insertion. To analyze the impact of this atypic mutational landscape, we constructed a complete structure of the omicron spike protein. Compared with the delta variant, the receptor-binding domain (RBD) of omicron has an increased electrostatic surface potential, but a decreased affinity for the ACE-2 receptor. The N-terminal domain (NTD) has both a decreased surface potential and a lower affinity for lipid rafts. The omicron variant is predicted to be less fusogenic and thus less pathogenic than delta, due to a geometric reorganization of the S1-S2 cleavage site. Overall, these virological parameters suggest that omicron does not have a significant infectivity advantage over the delta variant. However, in omicron, neutralizing epitopes are greatly affected, suggesting that current vaccines will probably confer little protection against this variant. In conclusion, the puzzling mutational pattern of the omicron variant combines contradictory properties which may either decrease (virological properties) or increase (immunological escape/facilitation) the transmission of this variant in the human population. This Janus-like phenotype may explain some conflicting reports on the initial assessment of omicron and provide new insights about the molecular mechanisms controlling its dissemination and pathogenesis worldwide.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据