In a significant step forward for treatment, scientists from the Gladstone Institutes and the Quantitative Biosciences Institute (QBI) at UC San Francisco (UCSF) have identified ways Ebola, Dengue and Zika viruses utilize the body’s cells, as well as a possible way Zika causes microcephaly in infants.
All tests were conducted using human cells, which scientists used to map each point of contact between viral and human proteins. Through the map, they are targeting those interactions and trying to kill the infection point by point, but they are also comparing each virus’s map, to find overlaps — those “weak points” most routinely targeted by multiple viruses.
“We’ve employed our systematic protein-protein interaction strategy on Ebola, Dengue, and Zika to get a better sense of how these three very problematic viruses hijack, rewire, and infect human cells,” said study lead Nevan Krogan, a senior investigator at the Gladstone Institutes, the director of QBI at UCSF, a professor of cellular and molecular pharmacology at UCSF, said. “To me, what’s most interesting is when we see the same human machinery being hijacked by seemingly very different viruses and different pathogenic proteins.”
While working to identify drugs that can fight off Ebola infections, Krogan said they have found key interactions — the question is whether they can capitalize on it for therapeutic value. Further, by comparing the three maps, scientists found one interaction that occurred in all. Those involved proteins play a critical role in some forms of cancer, and when the certain anti-cancer drugs were added to human and mosquito cells, they effectively wiped out both Dengue and Zika infections.
“We’ve developed an early-stage compound that has very potent antiviral activity against both Zika and Dengue in human and mosquito cells,” Jack Taunton, a professor in the Department of Cellular and Molecular Pharmacology at UCSF, said. “Now we need to tweak the molecule to optimize its safety and efficacy before it can be tested in patients.”
As to Zika, experiments also found that something key to human brain development — the ANKLE2 protein — may be what the disease inhibits to cause microcephaly, best known to people for the resulting abnormally small heads it causes in infants. Researchers are already thinking up ways to target ANKLE2 to develop microcephaly counters.