#1902 Remdesivir ameliorates ferroptotic renal injury in hamster after SARS-CoV-2 infection

Abstract

Abstract Background and Aims The purpose of this study was to see how remdesivir affected renal ferroptotic damage in hamsters following a human Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. We evaluated the inhibitory effects of remdesivir on the ferroptosis of SARS-CoV-2 infection in a hamster infection model and in in vivo assays. Method To investigate the effect of SARS-CoV-2 on renal ferroptosis, we administered 2.5 × 104 p.f.u. SARS-CoV-2 via intranasal to hamster. In the initial study, animals were treated with remdesivir subcutaneously (s.c.) for 7 days beginning at various times in relation to virus challenge. After 5 days, kidney tissues were harvested. The effect of REMDESIVIR on SARS-CoV-2 infection and ferroptosis were evaluated by immunohistochemistry. Next, ferroptosis-related markers, glutathione peroxidase 4 (Gpx4), 4-hydroxynonenal (4-HNE), Acyl-CoA synthetase long chain family member 4 (Acsl4), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (Ho-1) were evaluated by quantitative PCR. Results In hamsters, SARS-CoV-2 resulted in high viral protein expression in the renal tubules and decreased renal tubular luminal diameter in periodic acid-Schiff (PAS) stained kidney sections. Remdesivir treatment decreased SARS-CoV-2-induced viral spike protein, HO-1, ferritin heavy chain1 (FTH1), ferritin light chain (FTL), and 4-HNE expression in renal tubular epithelial cells of hamsters in a dose-dependent manner. GPX4 expression suppression after infection was ameliorated by remdesivir administration. Increased ferroptosis-related mRNA marker (Gpx4, 4-HNE, Acsl4, Nrf2, Ho-1) expression in hamster kidneys was suppressed by remdesivir treatment. Conclusion All of our data suggest that remdesivir treatment ameliorated SARS-CoV-2 infection-induced ferroptosis in the kidney in a hamster model.