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Virology: Repurposed influenza drug blocks SARS-CoV-2 transmission in ferrets

Nature Microbiology

December 3, 2020

A repurposed influenza drug can reduce the viral load of SARS-CoV-2 in the upper respiratory tract and suppress transmission of the virus in ferrets, suggests a paper in Nature Microbiology. The findings indicate that the drug MK-4482/EIDD-2801, which is currently in phase II/III clinical trials as a COVID-19 therapy, could be used to break community transmission of SARS-CoV-2.

Current therapies for COVID-19, such as remdesivir and reconvalescent serum, are ill-suited to controlling community transmission as they cannot be delivered orally. MK-4482/EIDD-2801 can be delivered orally and has been shown to prevent influenza transmission in a guinea pig model. Ferrets are a good model for studying SARS-CoV-2 as they transmit the virus efficiently but show minimal clinical signs, which resembles transmission in infected young-adult humans.

Richard Plemper and colleagues inoculated four sets of three ferrets with SARS-CoV-2. The ferrets were then treated twice daily with either 5 or 15 mg kg–1 of MK-4482/EIDD-2801 12 hours after infection, or 15 mg kg–1 of the drug 36 hours after infection. Ferrets treated with MK-4482/EIDD-2801 demonstrated substantially reduced levels of SARS-CoV-2 in the upper respiratory tract, whereas the control group carried a detectable virus burden in the nasal turbinates (passageways) 3.5 days after infection, and continued to be infectious until the study end. SARS-CoV-2 RNA was detectable in the nasal tissues of all animals but was significantly reduced in the groups treated with MK-4482/EIDD-2801.

The authors also assessed whether MK-4482/EIDD-2801 could suppress transmission of SARS-CoV-2. They inoculated two sets of three ferrets with SARS-CoV-2, with one set receiving MK-4482/EIDD-2801 12 hours after infection. Thirty hours after infection, the treated animals were housed individually with two uninfected animals for three days. After three days, infectious SARS-CoV-2 particles were not detected, including in the nasal tissues, in uninfected ferrets housed with animals treated with MK-4482/EIDD-2801. In contrast, the virus spread to all uninfected ferrets housed with untreated animals. These animals started producing infectious virus particles after 24 hours, and, by the end of the study, were reaching the peak replication stage of infection.

The authors caution that the antiviral efficacy of MK-4482/EIDD-2801 in humans is unknown. However, their findings indicate that this drug may have the potential to block transmission of SARS-CoV-2.

doi: 10.1038/s41564-020-00835-2

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