TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection

TLDR

Broad‑spectrum antivirals are needed for emerging coronaviruses, and TMPRSS2, a spike‑protein cleaving protease, is a promising therapeutic target. We examined the role of TMPRSS2 using animal models of SARS‑CoV and MERS‑CoV infection. TMPRSS2‑deficient mice were infected with SARS‑CoV and MERS‑CoV to assess airway pathology. Absence of TMPRSS2 in the airways reduces lung pathology after SARS‑CoV and MERS‑CoV infection, supporting its potential as a therapeutic target.

Abstract

Broad-spectrum antiviral drugs against highly pathogenic coronaviruses and other emerging viruses are desirable to enable a rapid response to pandemic threats. Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein, making it a potential therapeutic target for coronavirus infections. Here, we examined the role of TMPRSS2 using animal models of SARS-CoV and MERS-CoV infection. The results suggest that lack of TMPRSS2 in the airways reduces the severity of lung pathology after infection by SARS-CoV and MERS-CoV. Taken together, the results will facilitate development of novel targets for coronavirus therapy.