Monulpiravir (EIDD-2801): a new treatment?

SARS-CoV-2 is the virus responsible for COVID-19, which has caused a pandemic within several months of appearing. In order to develop effective drug therapies, it is necessary to understand the virus’ cycle, the mechanisms of cell infection, and to characterize the immune response. To study this latter, it is essential to have models for in vitro studies, but also in vivo, notably animal models that allow reproduction of natural human infection.  

Researchers at the University of North Carolina, Chapel Hill, USA, have developed a model of immunodeficient mice on which human pulmonary tissue was grafted so as to reproduce the diversity of cells that make up the lungs, which are targets for viral infection (notably fibroblasts, epithelial cells, and endothelials). Thanks to this model, virus replication and the pathogenesis of SARS-CoV-2 infection could be analysed in detail in vivo. The result: a potential new treatment was identified.

The researchers carried out histopathological analyses to shed light on tissue damage resulting from SARS-CoV-2 infection: in particular, desquamation of pneumocytes and formation of multi-nucleated cells. They showed, thanks to RNA-seq analysis (sequencing of transcripts, reflecting gene expression), the overexpression of the innate immune response during SARS-CoV-2 infection.

Finally, they unveiled an effective treatment that causes a reduction in viral replication: the EIDD-2801 molecule or Monulpiravir. This is an oral antiviral drug, already used against the flu virus. Monulpiravir is a  nucleoside analogue, incorporated into the viral genome during replication and introducing mutations deleterious to the virus. This molecule was also shown to allow significant reduction of SARS-CoV-2 after only 2 days of treatment. In addition, this antiviral also has a prophylactic effect, allowing reduction of viral replication in the pulmonary tissues and protection against tissue damage.