The Latest On The Rise Of Zika

The spread of the Zika virus is raising alarm bells in the United States, and Congress has yet to pass any legislation to combat the fight. Zika infections reported in Miami confirm the virus’ stateside arrival, pushing residents to take measures to protect their pregnancies from potentially devastating effects. In our previous issue, we explored the underpinnings of Zika: it is linked to microcephaly, in which babies are born with brains significantly smaller than normal.

New reports state the disease is sexually transmissible, persisting in those infected for up to six months. This has quickly turned into a public health crisis, with the FDA recently recommending universal testing of all donated blood across the US. As the wrath of Zika continues to migrate onward, today’s WEEKLY showcases the latest developments surrounding this mosquito-borne virus.

Zika On The Brain

Two recent studies on the basic science of Zika discuss how the virus may impact brain cells called human neuronal stem cells—the same cells found in developing fetal brains. Yale University (New Haven, CT) researchers demonstrated that the Zika virus infects lab-grown human neuronal stem cells, disrupting their reproduction and leading to cell death. By interacting with a cellular protein called TBK1, Zika prevents cells from organizing during cell division—suggesting a cause and effect for newborn microcephaly.

Adult brains maintain reserves of what are referred to as “neural progenitor” cells. These are stem cells that have begun the process of differentiating into neurons, and are found in the adult brain in specialized locations called “niches.” These progenitor cells play an important role in learning and memory. Researchers at Rockefeller University (New York City, NY) and La Jolla Institute for Allergy and Immunology (La Jolla, CA) demonstrated the virus infected adult neural progenitor cells in a mouse model in much the same way as seen with fetal stem cells. Since the brain is already fully developed, the impact may be much more subtle than the microcephaly cases seen in infants. Zika could potentially have an unappreciated impact on adult learning and memory.

Getting A Diagnosis

Developing a new diagnostic test and gaining FDA approval can take years—even a decade or more. In the case of a potential public health emergency, the FDA may grant Emergency Use Authorizations to make diagnostic tests available more quickly. In the past six months, the FDA has used this maneuver to authorize tests to detect either RNA (Zika’s genetic material) in early infections or to find the presence of anti-Zika antibodies in blood. The RNA-based tests may detect the virus much earlier during infection, but may have a higher incidence of a false negative, so antibody tests are advised to confirm the diagnosis. The RNA-based tests granted emergency authorization include:

  • Roche Molecular Systems’ (Rotkreuz, Switzerland) LightMix Zika rRT-PCR test.
  • Luminex Corporation’s (Austin, TX) xMAP MultiFLE Zika RNA assay.
  • Siemen’s Healthcare Diagnostics’ (Erlangen, Germany) Versant Zika RNA 1.0 Assay.
  • Viracor-IBT Laboratories’ (Lee’s Summit, MO) Zika Virus RT-PCR Test.
  • Hologic’s (Bedford, MA) Aptima’s Zika Virus Assay.
  • Altona Diagnostics’ (Hamburg, Germany ) RealStar ZIka Virus RT-PCR Kit.
  • Focus Diagnostics’ (Cypress, CA ) Zika Virus RNA Qualitative Real-Time RT-PCR.
  • Center For Disease Control’s (Atlanta, GA) Trioplex Real-time RT-PCR Assay.

The antibody-based tests granted emergency authorization include:

  • InBios International’s (Seattle, WA) ZIKV Detect IgM Capture ELISA.
  • Center For Disease Control’s Real-Time RT-PCR Assay.

Therapies On The Rise

While the current recommended treatment is rest and hydration, researchers at Yale found the hepatitis C virus (HCV) drug Sovaldi (Gilead; Foster City, CA) appeared to prevent Zika infection of cultured stem cells. Sovaldi or its derivatives may be a potential therapeutic or preventative treatment after additional clinical testing. This may seem surprising, but despite causing very different diseases, it turns out HCV and Zika come from the same family of viruses. They share structural similarities: both have a single strand of RNA as their genetic material, and both rely on an enzyme called an RNA-dependent RNA polymerase (RdRp) to replicate. Although the two RdRps are not identical, it is possible that since Sovaldi inhibits this enzyme in HCV it may also inhibit the RdRp in Zika.

Researchers at SRI International (Menlo Park, CA) are screening existing anti-viral compounds in hopes of unearthing a potential Zika therapeutic. In this case, the chemical library contains more than 3,000 members, including hundreds of anti-influenza compounds specifically targeting the influenza RdRp. Although not in the same family as Zika, influenza is also an RNA virus and relies on a RdRp for replication. According to Dr. Diane Beylkin, a lead scientist for the project, the RdRp enzyme makes an especially good target because it mutates less than other viral proteins, making resistance less likely to emerge. Dr. Beylkin’s team is developing a novel screening assay using a modified Zika virus which can replicate but is unable to assemble into new virus particles, enabling the measurement of replication (RdRp) inhibition without actually producing new virions. “It is very exciting to be collaborating with SRI’s experts on vector-borne diseases, biochemical assay development, and antiviral drug discovery on the development of a broad-spectrum antiviral drug for Zika virus,” says Beylkin. “We are going to need a combination of new antiviral drugs and vaccines to successfully control this emerging threat.”

A Prevention Convention

There are still no vaccines on the market, but Inovio Pharmaceuticals (San Diego, CA) recently announced a second round of clinical testing in Puerto Rico for its DNA-based Zika vaccine candidate. Its first round in June was the first test of a Zika vaccine on humans. Earlier in August, the National Institute of Health (Bethesda, MD) also began clinical testing of a DNA-based Zika vaccine. Several other companies are conducting preclinical studies of Zika vaccines, including Takeda (Osaka, Japan), GlaxoSmithKline (Brentford, UK), and Sanofi (Paris, France).

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