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Amino Acid Trio Blocks Zika’s Ability To Replicate

A novel formulation of multiple amino acids hinders the replication of Zika virus by up to 90% in human and non-human primate cells, a new study[1] indicates.

Researchers tested a unique composition of three free-form amino acids (FFAAP) — cystine, glycine, and glutamate, as well as a minute amount of selenium — that was previously known to increase biosynthesis (or production) of glutathione, an antioxidant, within cells.

It has previously been shown that intracellular glutathione adversely affects certain viruses[2], including HIV, suggesting that it could be an active cell defense. After working to successfully solubilize FFAAP, researchers analyzed its effects in human placental cells and Africa green monkey cells infected with Zika.

“We chose each of these cells because they lack the ability to produce interferon, a protein that could dampen replication of the virus. We wanted to allow the highest levels of Zika virus replication so that we could see how powerful the effect could be. In each of those cell lines, under controlled conditions, we found that FFAAP was enormously successful at suppressing Zika virus replication,”

says Julia Hilliard, a professor of biology at Georgia State University.

Replication Of Zika Virus

Results suggest Zika virus has cell-specific differences for replication. The researchers discovered that Zika needs glutathione in order to replicate in human placental cells, yet FFAAP treatment was still effective at virus inhibition.

This shows that the treatment does more than just increase intracellular glutathione biosynthesis. The investigators hope to pursue future studies to understand what other cellular processes are affected that result in Zika virus inhibition.

“Somehow, in spite of the fact that glutathione—a benefit to the virus—was increasing, the virus was suppressed nonetheless. That introduced the concept that FFAAP seems to have two mechanisms: it increases glutathione biosynthesis, but it seems to be doing something else independently to inhibit the virus, at least in human cells.”

says Hilliard.

Global Threat

Zika, which is primarily transmitted through Aedes aegypti mosquitos, can trigger the development of neurological conditions such as Guillain-Barré syndrome.

In pregnant women, Zika infection can contribute to miscarriage or preterm birth and cause infants to be born with congenital issues, including microencephaly, in which the baby’s head and brain do not develop properly. The virus can also linger in unique tissues and cells in the body after infection appears to be cleared.

Because there is no treatment or vaccine, the virus is a major public health concern. In 2015 and 2016, large outbreaks of Zika virus in North and South America led to the declaration of a public health emergency by the World Health Organization.

Hilliard and her colleagues plan to submit a grant application to study FFAAP’s mechanism of action, as well as other potential applications.

[1] Mugdha Vasireddi, et al. A novel antiviral inhibits Zika virus infection while increasing intracellular glutathione biosynthesis in distinct cell culture models. Antiviral Research; Volume 161, January 2019, Pages 46-52

[2] Nazzareno Ballatori, Suzanne M. Krance, Sylvia Notenboom, Shujie Shi, Kim Tieu, and Christine L. Hammond. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009 Mar; 390(3): 191–214.
doi: 10.1515/BC.2009.033