Structural basis of neutralized monoclonal antibody which recognizes multiple species of flavivirus

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02855
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: High Energy Accelerator Research Organization
• Principal Investigator: Kato Ryuichi 大学共同利用機関法人高エネルギー加速器研究機構, 物質構造科学研究所, 准教授 (50240833)
• Co-Investigator(Kenkyū-buntansha): 小澤 龍彦 富山大学, 学術研究部医学系, 准教授 (10432105) ; 正木 秀幸 近畿大学, 生物理工学部, 准教授 (90247982)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ウエストナイルウイルス / フラビウイルス / 中和抗体 / Ｘ線結晶構造解析

Outline of Final Research Achievements

West Nile virus (WNV) is a mosquito-borne human infectious virus of the Flavivirus family and sometimes causes lethal encephalitis and meningitis. We isolated interesting antibodies which neutralize both WNV and Japanese encephalitis virus (JEV) that also belongs to Flavivirus family. We determined the X-ray crystal structure of the complex of one of the antibodies and the enveloped protein of WNV at 2.6 A resolution. The three-dimensional structure and mutational analysis revealed that Arg388 which are conserved in JEV and WNV and CDR of L-chain are essential for the binding activity.

Free Research Field

構造生物学

Academic Significance and Societal Importance of the Research Achievements

２種類の抗原に活性を示すモノクローナル抗体の単離自体ユニークであり、それとWNVのエンベロープタンパク質複合体の立体構造解析は当然唯一無二である。明らかにした立体構造から分子認識機構を明らかにすることができ、それはフラビウイルスに共通の抗体医薬および合成低分子抗ウイルス薬の創薬を検討する上で重要な知見を与えると言える。