2025-09-11 理化学研究所,東京大学医科学研究所,滋賀医科大学
TMPRSS2抗体による全ての新型コロナウイルス変異株の感染阻止
<関連情報>
- https://www.riken.jp/press/2025/20250911_2/index.html
- https://www.cell.com/iscience/fulltext/S2589-0042(25)01685-2
ヒトTMPRSS2に対するモノクローナル抗体は、あらゆるSARS-CoV-2変異株による感染を防止する Monoclonal antibodies against human TMPRSS2 prevent infection by any SARS-CoV-2 variant
Michishige Harada ∙ Takehisa Matsumoto ∙ Mizuki Yamamoto ∙ … ∙ Mikako Shirouzu ∙ Jun-ichiro Inoue ∙ Takashi Saito
iScience Published:August 22, 2025
DOI:https://doi.org/10.1016/j.isci.2025.113424
Highlights
- Monoclonal antibodies (mAbs) against TMPRSS2 block SARS-CoV-2 infection in vitro
- TMPRSS2 mAbs inhibit infection of all variants of SARS-CoV-2 including Omicron
- mAbs target Spike/ACE2/TMPRSS2 interaction without inhibiting protease activity
- Animal models confirm in vivo inhibition of infection and inflammation by mAbs
Summary
The transmembrane serine protease 2 (TMPRSS2) plays a critical role in SARS-CoV-2 infection by priming the viral Spike (S) protein for host cell entry and thus represents a potential target for COVID-19 therapy. Here monoclonal antibodies (mAbs) against human TMPRSS2 were established for therapeutic application. In vitro infection by SARS-CoV-2 of cell lines and human lung organoids was strongly inhibited by the TMPRSS2 mAbs. These mAbs inhibited infection of all SARS-CoV-2 variants tested including omicron. mAbs recognized epitopes different from the enzymatic active site and did not inhibit protease activity, suggesting blockade of steric interactions of S protein-ACE2/TMPRSS2. The inhibitory activity of the mAbs in vivo was examined in human ACE2/TMPRSS2-double knock-in mouse and macaque models. Analysis of viral titers and histopathological analysis of the lung in these infected animals indicated that the TMPRSS2 mAb effectively suppressed viral titers and induction of inflammation in vivo.
