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Sirolimus + oseltamivir is a combination therapy consisting of sirolimus (also known as rapamycin), an mTOR inhibitor, and oseltamivir, a neuraminidase inhibitor antiviral. This combination has been investigated primarily for the treatment of severe influenza A (H1N1) infection. Sirolimus acts by inhibiting the mammalian target of rapamycin (mTOR) pathway, thereby modulating immune responses and reducing inflammation. Oseltamivir inhibits viral neuraminidase, preventing the release and spread of influenza virus from infected cells. Preclinical studies in mice have shown that delayed administration of this combination can protect against lethal H1N1 infection by attenuating lung injury through suppression of the mTOR-NF-κB-NLRP3 inflammasome-IL-1β axis, reducing proinflammatory cytokines and chemokines, decreasing inflammatory cell infiltration, lowering viral titers, and increasing autophagy[1][3]. Case reports suggest similar immunomodulatory effects in humans with severe influenza[2].
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