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SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801
Angela Wahl1,2,3, Lisa E Gralinski4, Claire E Johnson1,2,3
1International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nature
|February 9, 2021
Summary
Bats harbor coronaviruses capable of direct human transmission. A novel mouse model with human lung tissue efficiently replicates SARS-CoV-2, showing the antiviral EIDD-2801
Area of Science:
- Virology
- Infectious Diseases
- Immunology
Background:
- Coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2, often originate in bats.
- Bats host diverse coronaviruses with pandemic potential.
Purpose of the Study:
- To establish an experimental platform for studying in vivo coronavirus replication in human lung tissue.
- To investigate the potential for direct bat coronavirus transmission to humans.
- To evaluate therapeutic strategies for COVID-19.
Main Methods:
- Utilized immunodeficient mice implanted with human lung tissue (human lung-only mice, LoM).
- Inoculated LoM with SARS-CoV, MERS-CoV, SARS-CoV-2, and bat-derived SARS-like coronaviruses.
- Analyzed viral replication, cytopathic effects, and host immune responses in human lung tissue.
- Assessed the efficacy of EIDD-2801 for therapeutic and prophylactic treatment of SARS-CoV-2 infection.
Main Results:
- The LoM model demonstrated efficient in vivo replication of multiple human and bat coronaviruses without host or viral adaptation.
- SARS-CoV-2 predominantly infected human lung epithelial cells, including type-2 pneumocytes and ciliated airway cells.
- Infection induced significant cytopathic effects and a strong type-I interferon and inflammatory response.
- Administration of EIDD-2801 markedly inhibited SARS-CoV-2 replication in vivo.
Conclusions:
- Bats harbor endogenous coronaviruses capable of direct human transmission.
- The LoM model is a valuable platform for studying human lung infections by emerging coronaviruses.
- EIDD-2801 shows significant potential for preventing and treating COVID-19.
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