Structural study of beta-coronavirus particle formation mechanism

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15046
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: ZHANG ZHIKUAN 東京大学, 大学院薬学系研究科(薬学部), 助教 (60866937)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: ベータコロナウイルス / SARS-CoV-2 / Membrane protein / 粒子形成

Outline of Final Research Achievements

The outbreak of COVID-19 since the end of 2019 has not ended, and new infections and post-infection long COVID remain a significant public health crisis. Although research on the SARS-CoV-2, the cause of COVID-19, has been active worldwide, the virus particle formation mechanism was still largely unknown.
In this research, we used cryo-EM analysis to visualize the high-resolution three-dimensional structure and structural polymorphism of SARS-CoV-2 M protein, a structural protein required for the formation of SARS-CoV-2 virus particles. M proteins forms compact dimeric structures with two different conformations known as the long and short forms, respectively. These structures suggest that the structural polymorphism of M protein is important for the formation of SARS-CoV-2 particles medicated by M protein.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

SARS-CoV-2は終息しておらず、今後も人類と共存する病原体の一種である。現在、プロテアーゼ阻害剤やSタンパク質を発現させたmRNAワクチンなどの治療・予防方法が主に開発が進められてきたが、その変異株が既存の治療法を迅速に無効化するという懸念がある。よって、より多面的な治療手法の開発が必要であり、ウイルスの粒子形成に重要な役割を果たすMタンパク質は可能性のある創薬標的である。本研究で可視化されたのMタンパク質の3次元構造は、今後Mタンパク質を標的とする創薬の構造基盤を提供している。