Angiotensin-(1–7) decreases inflammation and lung damage caused by betacoronavirus infection in mice
摘要
Pro-resolving molecules, including the peptide Angiotensin-(1–7) [Ang-(1–7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1–7) in betacoronavirus infection in mice.
MethodsC57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1–7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1–7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated.
ResultsAng-(1–7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1–7) during MHV infection. Ang-(1–7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1–7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates.
ConclusionAng-(1–7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.
Graphical Abstract