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?:abstract
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Since its emergence in Wuhan, China in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide resulting in a global pandemic with >2 million deaths within a year of the emergence of the virus. In the search for small molecule inhibitors of SARS-CoV-2 Molnupiravir (EIDD-2801), an orally bioavailable nucleoside analog that was originally developed as an antiviral against influenza viruses but that exerts also activity against a number of other RNA viruses, including SARS-CoV2 and other coronaviruses. We here report on the effect of EIDD-2801 in a well-established Syrian hamster SARS-CoV-2 infection model. Oral treatment of SARS-CoV-2-infected hamsters with EIDD-2801 for four consecutive days, starting from the day of infection, significantly reduced infectious virus titers and viral RNA loads in the lungs and markedly improved lung histopathology in a dose-dependent manner when assessed at 4 dpi. When onset of treatment with 500 mg/kg/dose was delayed until 24h post-infection, a modest but significant antiviral effect was observed. When suboptimal doses of both favipiravir (300 mg/kg, BID) and EIDD-2801 (150 mg/kg, BID) were combined, a complete reduction (∼5 log10) of infectious virus titers was observed in the lungs of most of the combo-treated animals whereas either compound alone resulted in a reduction of respectively 1.2 and 1.3 log10. The potential of EIDD-2801 for the treatment and/or prevention of SARS-CoV-2 alone or in combination with favipiravir deserves further attention.
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