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bioRxiv · 10.64898/2026.02.23.707600

AVE0991, a Mas receptor agonist, increases influenza and COVID-19 severity in vivo.

Wu, M.·Sng, J. D. J.·Noye, E. C.·McCallum, G.·Bielefeldt-Ohmann, H.·Foo, C. X.·Ronacher, K.·Chew, K. Y.·Short, K. R.
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Abstract

Dysregulation of the renin-angiotensin system (RAS) contributes to severe influenza and COVID-19, potentially via impaired ACE2/Ang-(1-7)/Mas receptor (MasR) signalling. AVE0991, an orally bioavailable MasR agonist, protects against non-infectious lung inflammation, but its effects in viral respiratory disease are unknown. We evaluated AVE0991 in human lung epithelial cells and murine models of influenza A virus (IAV) and SARS-CoV-2 infection. In vitro, AVE0991 suppressed cytokines IL-6 and TNF- to both IAV and SARS-CoV-2 and reduced IAV titres. Unexpectedly, in vivo treatment worsened disease. These findings highlight discordant in vitro and in vivo effects and underscore the need for careful evaluation of RAS-targeted therapies in acute viral infection.

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Wu, M., Sng, J. D. J., Noye, E. C., McCallum, G., Bielefeldt-Ohmann, H., Foo, C. X., Ronacher, K., Chew, K. Y., Short, K. R.. 2026-02-24. AVE0991, a Mas receptor agonist, increases influenza and COVID-19 severity in vivo.. https://doi.org/10.64898/2026.02.23.707600

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