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Friday, 26 January 2018

Repurposed drug effective for Zika virus


In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus and blocked transmission of the virus to mouse fetuses. Researchers at University of California San Diego School of Medicine, with colleagues in Brazil and elsewhere, say their findings support further investigation of using the repurposed drug as a potential treatment for Zika-infected adults, including pregnant women.

 Zika infection during the first trimester confers the greatest risk of congenital microcephaly. Outbreaks of Zika virus in Brazil in 2015 and 2016 were marked by an increased incidence of newborns with congenital malformations, most notably undersized heads (microcephaly) and significant neurological abnormalities.

A great deal of research has focused on the pathology of Zika infections, including earlier work by the Muotri lab and collaborators that described how the virus is transmitted from mother to fetus by infecting cells that, ironically, will later develop into the brain's first and primary form of defense against invasive pathogens.

In its latest work, however, the Muotri lab sought clinical solutions. The team investigated an antiviral drug called sofosbuvir, approved and marketed under the brand name Sovaldi to treat and cure hepatitis C infections. The drug works by inhibiting replication of the hepatitis C virus; researchers noted that both hepatitis C and Zika belong to the same viral family and bore strong structural similarities that could make sofosbuvir effective against the latter. In addition, it had been reported that sofosbuvir was protective against Zika in different cell types.

In tests using human neural progenitor cells (NPCs)-self-renewing, multipotent cells that generate neurons and other brain cell types-the scientists found that exposure to sofosbuvir not only rescued dying NPCs infected with the Zika virus, but restored gene expression linked to their antiviral response. In subsequent tests using an immunodeficient mouse model infected by Zika, intravenous injections of sofosbuvir significantly reduced viral loads in blood serum compared to a placebo group.

Fetuses of Zika-infected pregnant mice did not show detectable Zika virus amplification in the sofosbuvir-treated group. This shows that the drug was well-tolerated by the Zika-infected pregnant mice and that it was able to arrest Zika replication in vivo and stop transmission from mother to fetus.
          haleplushearty.blogspot.com

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