Professor Takeda gave a lecture at TWINCORE in Germany on Monday, March 9, 2026.

https://twincore.de/

https://twincore.de/events/seminar-takeda

Host protease-mediated activation of respiratory viruses: From the laboratory bench to the frontlines of infectious disease control

Respiratory viral membrane fusion proteins are activated through cleavage by host proteases. We have long pursued research aimed at identifying the host proteases responsible for this activation process. In this context, we focused on TMPRSS2, a type II transmembrane serine protease. In addition to the apparent compatibility between the cleavage sequences of many viral fusion proteins and the substrate specificity of TMPRSS2, our interest was strongly motivated by the fact that this protease is itself a membrane protein localized within the same cellular membrane environment as viral fusion proteins. As a result, we demonstrated that TMPRSS2, as originally hypothesized, plays a critical role in the establishment of infection and the expression of pathogenicity of a wide range of respiratory viruses.

Subsequently, Vero cells expressing TMPRSS2 were shown to exhibit extremely high susceptibility to SARS-CoV-1 and MERS-CoV, and TMPRSS2 was further demonstrated to be an essential factor for the pathogenicity of these viruses. However, the international transfer of Vero cells is subject to regulations under the Convention on International Trade in Endangered Species (CITES) and is not straightforward. Therefore, from the perspective of establishing a global research infrastructure for coronavirus studies, we proceeded to build a framework that would enable international distribution of these cells.

During this process, the SARS-CoV-2 pandemic emerged. As anticipated, VeroE6/TMPRSS2 cells exhibited exceptionally high susceptibility to SARS-CoV-2. During the early phase of the pandemic, these cells were distributed to several hundred research institutions worldwide and were widely utilized in global SARS-CoV-2 countermeasures.

In this seminar, we will present these experiences together with subsequent advances arising from our foundational research.