SARS-CoV-2とSARS-CoVの受容体結合領域に高度に保存された暗号的エピトープ

Meng Yuan¹, Nicholas C Wu¹, Xueyong Zhu¹

¹Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Science (New York, N.Y.)

|April 5, 2020

まとめ

中和抗体であるCR3022は,SARS-CoV-2のスパイクタンパク質の保存された領域に結合する. この交互反応結合は,コロナウイルスの抗体認識に関する洞察を提供します.

科学分野:

ウイルス学
免疫学
構造生物学

背景:

SARS-CoV-2によって引き起こされるCOVID-19のパンデミックは,ウイルス抗原性を理解する必要性を強調しています.
SARS-CoV-2 と中和抗体の間の特定の相互作用に関する知識は限られている.

研究の目的:

SARS-CoV-2のスパイクタンパク質受容体結合領域 (RBD) に結合するCR3022抗体の構造的基礎を決定する.
SARS-CoV-2とSARS-CoVの抗体間のクロス反応の可能性を調査する.

主な方法:

3. 1 アングストロムの解像度で,SARS-CoV-2 RBDとの複合体における CR3022 抗体の構造を決定するために,X線結晶学を使用した.
抗体のスパイクタンパク質への結合エピトープのアクセシビリティを分析するために,構造モデリングを使用した.

主要な成果:

結晶構造は,CR3022が,ACE2受容体結合部位とは異なる,SARS-CoV-2 RBD上の保存されたエピトープを標的としていることを明らかにした.
CR3022は,SARS-CoV-2とSARS-CoVの両方に交互反応性結合を示した.
構造モデリングは,トリメアスパイクタンパク質の少なくとも2つのRBDが"上"の形状にある場合にのみエピトープにアクセス可能であることを示した.

結論:

CR3022は,SARS-CoV-2の抗体認識に関する分子理解を提供します.
CR3022が標的とした保存された交互反応性エピトープは,広範なコロナウイルス治療の標的となる可能性があります.

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