The Register Citizen (Torrington, CT)
Drug may fight off Zika in pregnant women
Yale researchers discover existing, approved product
NEW HAVEN >> An existing approved drug may stop the Zika virus from hindering brain development in the human fetus, preventing the catastrophic birth defect microcephaly, according to research reported Wednesday by Yale scientists.
The drug, Sofosbuvir, is approved by the Food and Drug Administration to treat chronic hepatitis C infections. The research was reported Wednesday in the journal Cell Reports.
Microcephaly, which causes abnormally small heads and underdeveloped brains in fetuses, occurs because the Zika virus kills stem cells in the brain, which are responsible for cell division, according to a press release. Sofosbuvir appears to stop the virus from doing damage, allowing cell division to continue.
“There is an urgent need to identify therapeutic approaches to halt Zika infection, especially in pregnant women,” said Marco Onorati, co-first author of the paper, in the release. Onorati is a researcher in the lab of senior author Nenad Sestan, professor of neuroscience, comparative medicine, genetics and psychiatry. “In the interim, we hope these findings can lead to therapies that might minimize the damage caused by this virus,” Onorati said.
What happens in the developing fetal brain, according to Andre M.M. Sousa, another co-first author, is that a protein expressed by the stem cell, TBK1, which promotes cell division, is diverted to another location in the cell to try to fight the virus. “It actually starts a process that will cause cell death when it moves to another part of the cell,” Sousa said.
“It’s a lose-lose situation.”
The therapeutic action of Sofosbuvir was confirmed in the laboratory and has not been tested in human clinical trials. However, Onorati said, “since this drug is approved and safe for humans … basically the trials are faster, so that’s one advantage of this drug.”
“Our research focuses on understanding why and how Zika virus infection affects the developing human brain and causes such devastating outcomes, including microcephaly,” Onorati said. “We identified a central mechanism that explains why neural stem cells or progenitor cells, the founder for nearly all of the cells and cell types in the adult brain, are so susceptible to Zika infection.”
It is too early to recommend that Sofosbuvir be given to pregnant women, Onorati said, though there were no side effects in tests on mice in the lab. “Additionally, while our data suggest the use of Sofosbuvir against Zika virus may have a positive effect in vitro, there is not yet enough data to support its usage,” Onorati said.
The results of the research also may be applied to microcephaly caused by infections other than Zika, he said. Human cytomegalovirus and rubella also can cause the birth defect. “We believe we have put forward a plausible and testable hypothesis about the Zika viral infection mechanism through meticulous observation and experimentation in models of neural stem cells close to those present in our developing brain,” Onorati said.
The Zika virus, spread by two species of mosquitoes and by sexual relations, has hit dozens of countries and U.S. territories in the Caribbean, Latin America, Pacific islands and Cape Verde in Africa, according to the Centers for Disease Control and Prevention. Cases also have been found in Miami and the Tampa Bay area, where mosquitoes are suspected as the cause. Males and non-pregnant females suffer only mild flu-like symptoms, if any, from the virus.
Onorati called the study “a truly remarkable demonstration of multidisciplinary collaboration among the scientific community,” including “neuroscientists, clinical researchers, stem cell biologists and virologists, not just here at Yale University but also from other laboratories within the U.S. and around the globe. The altruistic contribution of all parties made it possible for us to accomplish such a tremendous discovery in a relatively short period of time. We are very grateful for that.”