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

Melanie Wu; Julian D. J. Sng; Ellesandra C. Noye; Georgina McCallum; Helle Bielefeldt‐Ohmann; Cheng Xiang Foo; Katharina Ronacher; Keng Yih Chew; Kirsty Renfree Short

doi:10.64898/2026.02.23.707600

MicrobiologybioRxivFeb 24, 2026

Preprint

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

Melanie Wu iD, Julian D. J. Sng iD, Ellesandra C. Noye iD, Georgina McCallum iD, Helle Bielefeldt‐Ohmann iD, Cheng Xiang Foo iD, Katharina Ronacher iD, Keng Yih Chew iD, Kirsty Renfree Short iD

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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