杭州市科学技术协会

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains a large number of amino acid mutations and is listed as the latest mutant of concern (VOC) by the World Health Organization. At present, it has spread to more than 100 countries and regions, leading to governments introducing a fresh wave of quarantine measures. Understanding the structures of key Omicron proteins could be essential in limiting the spread and the development of corresponding vaccines and drugs.

A team from the Shanghai Jiao Tong University has acquired highly accurate structures of the spike (S), membrane (M), and nucleocapsid (N) proteins of the Omicron variant by use of the AlphaFold2 algorithm from deepmind. The study was published in Research, where the team of scientists has potentially uncovered the underlying immune escape mechanism displayed by the Omicron strain so far. Research is the first Science Partner Journal recently launched by the American Association for the Advancement of Science (AAAS) in collaboration with the China Association for Science and Technology (CAST).

“SARS-CoV-2 is constantly mutating,” said Professor Yongyong Shi, who led the study. “AlphaFold2 is a powerful computational tool that can be used to accurately determine protein structure. We acquired these structures within 2 days of the publication of the omicron genome sequence on the GISAID databases and the predicted structures have been published online and available since December 8, 2021.”

“Spike protein RBD plays an important role in SARS-CoV-2 binding with the ACE2 receptors,” Professor Shi added. “Our findings suggest that the mutations present in the Omicron variants may influence the interaction between the Omicron RBD and ACE2, which could be responsible for the recent surge in infections observed globally. On a positive note, we also found that the conserved RBD epitope recognized by antibody S309 was not changed in the Omicron RBD, which should allow for the continued use of antibody S309 in the treatment of the Omicron variant as well.”

Moreover, the Omicron S1 NTD structures display significant differences from the original strain. The epitope on the Omicron S1 NTD targeted by antibody 4A8 was significantly changed, which suggested that the effectiveness of 4A8 and other antibodies targeting this epitope could be reduced. The mutations on the Omicron S1 NTD may increase immune escape rates and decrease the effectiveness of the existing vaccines. In other words, these mutations on S1 NTD are worthy of attention.

“Our work demonstrates the effectiveness of high-precision structural simulation using the AlphaFold2 algorithm, which can quickly obtain the key structures of different variants, providing first-hand information for the fighting at the front lines of the pandemic.” Shi also stressed. “Such computational predictions can be used in conjunction with experimental results to hasten the development of drugs and vaccines. Our work can be a model for initial studies of new mutant strains that may arise in the future.”

IMAGE: The S, M, and N proteins’ structures of SARS-CoV-2 Omicron variant.

CREDIT: Yongyong Shi

Original source:

Qiangzhen Yang, Ali Alamdar Shah Syed, Aamir Fahira, Yongyong Shi, "Structural Analysis of the SARS-CoV-2 Omicron Variant Proteins", Research, vol. 2021, Article ID 9769586, 4 pages, 2021.

Tag: Information Science

Source: https://doi.org/10.34133/2021/9769586