Title of paper: The respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids

Authors: Masatoshi Kakizaki, Rina Hashimoto, Noriyo Nagata, Takuya Yamamoto, Takashi Okura, Hiroshi Katoh, Yuki Kitai, Yukiko Akahori, Kazuya Shirato, Akihide Ryo, Kazuo Takayama, and Makoto Takeda

Journal: Journal of Virology

Volume/page: in press

The infection of SARS-CoV-2 requires activation of the viral spike protein by host proteases. The type II transmembrane serine protease, TMPRSS2, has been shown to be critically important for SARS-CoV-2 infection in lung epithelial Calu-3 cells and in murine airways. In this study, analyses were conducted using human respiratory organoids with TMPRSS2 gene knockout. The findings suggest that, in the replication of SARS-CoV-2 in human respiratory organoids, various proteases, including TMPRSS2, other serine proteases, and cathepsins, contribute significantly. Therefore, SARS-CoV-2 infection in human respiratory tissues is considered to be more complex than what has been observed in cell lines or mice.