Virology: Drug treats and prevents SARS-CoV-2 infection in humanized mice

Oral administration of an antiviral drug, EIDD-2801, in immunodeficient mice transplanted with human lung tissue inhibits SARS-CoV-2 replication and can prevent infection, reports a paper published online in Nature. The study also finds that two SARS-like bat coronaviruses are capable of replicating in the humanized mouse model, suggesting that bats may harbour coronaviruses that are potentially capable of direct transmission to humans.

Using mice implanted with human lung tissue, Victor Garcia and colleagues demonstrate that SARS-CoV, MERS-CoV and SARS-CoV-2 can replicate in their model. The authors also found that two SARS-like bat coronaviruses (WIV1-CoV and SHC014-CoV) were able to replicate in the lung tissue without any prior adaptation. This finding would suggest that bats harbour coronaviruses that are capable of being directly transmitted to humans, bypassing the need for further adaptation in an intermediary host.

In addition, Garcia and co-authors evaluated the effectiveness of the broad-spectrum antiviral drug EIDD-2801 as a treatment for COVID-19 in mice. The drug was administered 24 and 48 hours after SARS-CoV-2 exposure, and the authors found that EIDD-2801 significantly reduced the number of infectious virus particles in the mice. A greater reduction in virus levels was seen in mice that started to receive the treatment 24 hours after exposure, compared to those that received the drug 48 hours after infection. When EIDD-2801 was administered to mice 12 hours before SARS-CoV-2 exposure, the drug was observed to prevent infection.

The authors note that compared to other treatments currently in use against SARS-CoV-2 (such as remdesivir, convalescent plasma and monoclonal antibodies), which require administration in clinical settings, EIDD-2801 can be taken orally and has the potential for more widespread use. The findings support the development of this drug, which is currently undergoing phase II and phase II/III clinical trials, as a potential treatment for COVID-19.