A team of U.S. researchers has found an antibiotic that blocks potential routes of Zika virus infection of the developing fetus, at least in human cell culture.
The antibiotic, called duramycin, is able to block the virus from replicating in cells that are thought to transmit it along two routes: a placental route established in the first trimester of pregnancy, and a route across the amniotic sac that becomes available only in the second trimester.
The researchers at University of California, San Francisco, and University of California, Berkeley, reported their findings about the possible routes of Zika virus infection and the results of laboratory tests of the older-generation antibiotic's effects on human tissue in the journal Cell Host & Microbe published on Monday.
Co-author Eva Harris, a professor of infectious diseases and vaccinology at UC Berkeley' s School of Public Health, said "our paper shows that duramycin efficiently blocks infection of numerous placental cell types and intact first-trimester human placental tissue by contemporary strains of Zika virus recently isolated from the current outbreak in Latin America."
Zika virus, spread by mosquitoes and linked to a fetal deformity called microcephaly as well as Guillain-Barré syndrome in adults, has been throughout South and Central America and is heading toward the southern United States. Microcephaly, presumably caused when the virus crosses from an infected mother to the growing fetus in the first two trimesters of pregnancy, is characterized by a small head and serious brain damage.
"Very few viruses reach the fetus during pregnancy and cause birth defects," said Lenore Pereira, a virologist and professor of cell and tissue biology at the UCSF School of Dentistry. "Understanding how some viruses are able to do this is a very significant question and may be the most essential question for thinking about ways to protect the fetus when the mother gets infected."
Examining the Zika virus in isolated cells and intact tissue explants, the researchers found it to infect several different placental cell types, including cell types within the placenta and outside the placenta in the fetal membranes, and the epithelial cells of the amniotic membrane surrounding the fetus were particularly susceptible to virus infection.
"This suggests that these cells play a significant role in mediating transmission to the fetus and supports the hypothesis that transmission could occur across these membranes independently of the placenta, especially in mid- and late gestation," Pereira said. "The most severe birth defects associated with Zika infection - like microcephaly - seem to occur when a woman is infected in the first and second trimester."
However, the researcher noted that "there may be a range of lesser but still serious birth defects that occur when a woman is infected later in pregnancy."
Duramycin is an antibiotic that bacteria produce to fight off other bacteria. It is commonly used in animals and is in clinical trials for people with cystic fibrosis, according to a news release from UC Berkeley. Recent studies have shown it to be effective in cell culture experiments against dengue and West Nile virus, which are flaviviruses like Zika, as well as filoviruses, like Ebola.
The study "indicates that duramycin or similar drugs could effectively reduce or prevent transmission of Zika virus from mother to fetus across both potential routes and prevent associated birth defects," said Pereira.
