Zika fever (also known as Zika virus disease and simply Zika) is an infectious disease caused by the Zika virus, which is spread mostly by the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus) or through sex. These mosquitoes are aggressive daytime biters. .It also can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause certain birth defects such as microcephaly, characterized by an abnormally small head, and other neurological disorders in newborns. Most cases have no symptoms, but when present they are usually mild and can resemble dengue fever. Symptoms may include fever, red eyes, joint pain, headache, and a maculopapular rash.

First identified in Uganda in 1947 in monkeys and later identified in humans in 1952, the first large outbreak of disease caused by Zika infection was reported from the Island of Yap in 2007, but it garnered little scientific interest until an outbreak began in South America in mid-2015. This outbreak is now known to be responsible for an increase in cases of microcephaly — a severe birth defect in which afflicted infants are born with underdeveloped brains.

 In the continental United States, there have been a total of 2,260 reported cases of Zika. Though most cases are associated with travel, 43 cases of local transmission have been reported in Florida, in the Miami area. In addition, Puerto Rico has reported 7,855 locally transmitted cases.

To combat further spread of the virus, many research groups are fast tracking the development of vaccines, treatments and mosquito control measures.

A team of researchers from Florida State University, Johns Hopkins University and the National Institutes of Health has found two groups of existing drug compounds that can treat Zika virus infections in two ways. One way stops the virus replicating in the body, and the other way stops the virus activity in fetal brain cells that leads to birth defects in newborns.

For their new work, the team developed a drug repurposing screen, a relatively new method that researchers are using to speed up drug development. They screened 6,000 existing compounds currently in late-stage clinical trials or already approved for human use for other conditions, and identified several compounds that showed the ability to hinder or halt the progress of the Zika virus in lab-grown human neural cells.

The new findings are an extension of previous work by the research team, which found that Zika mainly targets specialized stem cells that give rise to neurons in the brain's outer layer, the cortex. The researchers observed Zika's effects in two- and three-dimensional cell cultures called "mini-brains," which share structures with the human brain and allow researchers to study the effects of Zika in a more accurate model for human infection. In the current study, the research team exposed similar cell cultures to the Zika virus and the drugs one at a time, measuring for indicators of cell death, including caspase-3 activity, a chemical marker of cell death, and ATP, a molecule whose presence is indicative of cell vitality.

Further analysis of the surviving cells, showed that the promising drugs could be divided into two classes: neuroprotective drugs, which stop the virus carrying out cell-damaging "caspase-3 activity" in human cortical neural progenitors – precursors to brain cells in fetal development. and antiviral drugs, which slow or stop viral infection or replication. 

Overall, three drugs showed robust enough results to warrant further study: PHA-690509, an investigational compound with antiviral properties; emricasan, now in clinical trials to reduce liver damage from hepatitis C virus and shown to have neuroprotective effects; and niclosamide, a drug already used in humans and livestock to combat parasitic infections, which worked as an antiviral agent in these experiments.

Niclosamide can safely treat parasites in the human gastrointestinal tract, but scientists have not yet determined if the drug can even penetrate the central nervous system of adults or a fetus inside a carrier's womb to treat the brain cells targeted by Zika.They don’t even know if the drugs would address the wide range of effects of Zika infection include microcephaly in fetuses and temporary paralysis from Guillain-Barre syndrome in adults. Additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,

The new study, published in Nature Medicine, is a breakthrough because it means effective treatments for Zika could be just around the corner, without having to wait the many years it normally takes to develop a new drug from scratch.

As Prof. Hongjun Song, Johns Hopkins University School of Medicine, Baltimore, MD said: It takes years if not decades to develop a new drug. In this sort of global health emergency, we don't have time. So instead of using new drugs, we chose to screen existing drugs. In this way, we hope to create a therapy much more quickly."

COPYRIGHT: This article is property of We Speak Science, a non profit institution co-fonded by Dr. Detina Zalli (Harvard University) and Dr. Argita Zalli (Imperial College London). The article is written by Detina Zalli and Brisilda Pashaj (University of Plovdiv, "Paisii Hilendarski " Bulgaria ( Msc. Medical Biology).

 

REFERENCES:

  1. http://www.who.int/emergencies/zika-virus/timeline/en/
  2. http://www.who.int/mediacentre/factsheets/zika/en/
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