Repurposed drug found to be effective against 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. Writing in the current online issue of the journal Scientific Reports, 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.

"There has been a lot of work done in the past year or so to address the Zika health threat. Much of it has focused on developing a vaccine, with promising early results," said senior author Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.

"But there is also a great need to develop clinical strategies to treat Zika-infected individuals, including pregnant women for whom prevention of infection is no longer an option. They represent the greatest health crisis because a 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. Moreover, fetuses of Zika-infected pregnant mice did not show detectable Zika virus amplification in the sofosbuvir-treated group.

"This suggests that one, the drug was well-tolerated by the Zika-infected pregnant mice and two, more importantly, that it was able to arrest Zika replication in vivo and stop transmission from mother to fetus," said Muotri.

The researchers emphasize that their findings are preliminary, with much more work to be done. "But they also illustrate the immediate translational potential of repurposing a drug that is already in wide clinical use for a similar viral infection," Muotri said. "Until there is approval of a Zika vaccine, we think this is an approach that needs to be pursued whole-heartedly."

Pinar Mesci, Angela Macia, Spencer M Moore, Sergey A Shiryaev, Antonella Pinto, Chun-Teng Huang, Leon Tejwani, Isabella R Fernandes, Nicole A Suarez, Matthew J Kolar, Sandro Montefusco, Scott C Rosenberg, Roberto H Herai, Fernanda R Cugola, Fabiele B Russo, Nicholas Sheets, Alan Saghatelian, Sujan Shresta, Jeremiah D Momper, Jair L Siqueira-Neto, Kevin D Corbett, Patricia C B Beltrão-Braga, Alexey V Terskikh, Alysson R Muotri.
Blocking Zika virus vertical transmission.
Scientific Reports 8, Article number: 1218 (2018). doi: 10.1038/s41598-018-19526-4

Most Popular Now

In wine, there's health: Low levels of alcohol goo…

While a couple of glasses of wine can help clear the mind after a busy day, new research shows that it may actually help clean the mind as well. The new study, which appe...

Sanofi to acquire Ablynx for €3.9 Billion

Sanofi and Ablynx, a biopharmaceutical company engaged in the discovery and development of Nanobodies®, entered into a definitive agreement under which Sanofi will offer ...

Repurposed drug found to be effective against Zika…

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 transmiss...

Interim publications of randomized trials make new…

Early results from randomized trials are sometimes published before the trial is completed. The results of such interim publications may generate a great deal of interest...

Drug trial protocol redactions by industry sponsor…

New research published by the Journal of the Royal Society of Medicine exposes the extent of redactions in protocols for industry-sponsored randomised drug trials. Trial ...

Advanced Accelerator Applications receives FDA ap…

Novartis AG (NYSE: NVS) announced that Advanced Accelerator Applications, a subsidiary of Novartis Groupe S.A., has received US Food and Drug Administration (FDA) approva...

Blood vessel-on-a-chips show anti-cancer drug effe…

Researchers at the Institute of Industrial Science (IIS), the University of Tokyo, CNRS and INSERM, report a new organ-on-a-chip technology for the study of blood vessel ...

Guidelines extended to improve the use of feedback…

Researchers have recommended changes to international guidelines used in the development of clinical trials in an effort to gain information about the impact of the treat...

Brilinta significantly reduces CV events and coron…

AstraZeneca today announced results from a new sub-analysis of the Phase III PEGASUS-TIMI 54 trial, demonstrating a risk reduction of 19% in MACE (the composite of CV dea...

Roche reports good results in 2017

In 2017, Group sales rose 5% to CHF 53.3 billion. Core operating profit grew 3% and Core EPS increased 5%, reflecting the good underlying business performance. On an IFRS...

FDA approves new treatment for certain digestive t…

The U.S. Food and Drug Administration today approved Lutathera (lutetium Lu 177 dotatate) for the treatment of a type of cancer that affects the pancreas or gastrointesti...

How old antibiotic compounds could become tomorrow…

As the fight against drug-resistant infections continues, University of Leeds scientists are looking back at previously discarded chemical compounds, to see if any could ...

Pharmaceutical Companies

[ A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Z ]