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Updated: Sep 6, 2025

Engineering Antiviral Agents via Surface Plasmon Resonance

Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

ウイルスの進化過程におけるSARS-CoV-2受容体結合領域における変異的制約の変化

Tyler N Starr¹, Allison J Greaney^1,2,3, William W Hannon^1,4

¹Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Science (New York, N.Y.)

|June 28, 2022

まとめ

SARS-CoV-2の変種は,スパイクタンパク質の受容体結合領域 (RBD) の変異によって進化する. これらの変化は,エピスタシスの影響を受け,ウイルスの進化と抗体の脱出を形作り,オミクロンのような将来の株に影響を与えます.

科学分野:

ウイルス学
分子生物学
遺伝学

背景:

深刻な急性呼吸器症候群のコロナウイルス2型 (SARS-CoV-2) は,ACE2結合と抗体認識に影響を与えるスパイク受容体結合領域 (RBD) 置換を示す.
これらの置換は,ある部位での突然変異が他の部位での突然変異の影響を変化させるエピスタシスを通して,将来のウイルスの進化に影響を与える可能性があります.

研究の目的:

SARS-CoV-2の進化の形成におけるエピスタシスの役割を調査する.
様々なSARS-CoV-2変種 (Wuhan-Hu-1,Alpha,Beta,Delta,Eta) のRBDにおけるすべての単一のアミノ酸変異が,ACE2結合に与える影響を測定する.

主な方法:

特定のSARS-CoV-2のRBDにおけるすべての単一アミノ酸置換の影響を評価するために,深層変異スキャニングを使用した.
分析は,ヒトのアンジオテンシン変換酵素2 (ACE2) 受容体への結合 afinity の変化に焦点を当てた.

主要な成果:

特定の置換物,特にAsn501Tyr (N501Y) は,他の部位での変異の影響を変化させ,エピスタティックシフトを誘発した.
これらのエピスタティックシフトは,オミクロン変異種に見られる抗体脱出変異を含む,後の進化的変化を促進すると観察されました.
RBDの全体的な構造が保存されているにもかかわらず,エピスタティック効果は明らかでした.

結論:

エピスタシスは,SARS-CoV-2の進化軌跡において決定的な役割を果たし,結合性や免疫回避性を持つ変種の出現に影響を与えます.
RBDにおけるこれらの配列-機能関係を理解することは,進行中のウイルス進化を解釈し,将来のSARS-CoV-2適応を予測するために不可欠です.

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Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

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