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Zika on the Brain

by | Aug 28, 2023 | Biotech for Non-Scientist

Hey folks, remember when Zika had us all on edge back in 2016? Well, it’s time for an update because this pesky virus is still making headlines, and not in the U.S. but globally. From new outbreaks in places like Kerala, India, to fresh research that shows it’s not just pregnant women who need to be cautious—yes, it can be sexually transmitted too—Zika remains a hot topic. While scientists are hustling to find a cure or vaccine, we’re here to give you the latest scoop on what you need to know about Zika’s symptoms, risks, and how to stay safe. So, let’s dive in!

ZIKA ON THE BRAIN

Two studies in 2016 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 2016, the FDA used this maneuver to authorize tests to detect either RNA (Zika’s genetic material) in early infections or to find anti-Zika antibodies in the 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
  • Arup Laboratories’ (Salt Lake City, UT) RT-PCR Test
  • Abbott Molecular Inc. (Des Plaines, IL) Abbott RealTime Zika
  • Nanobiosym’s (Cambridge, MA) Gene-RADAR Zika Virus Test

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 that 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.”

In the ongoing battle against the Zika virus, researchers are leaving no stone unturned. One of the most promising studies in this area was published in 2022 by a team primarily affiliated with the University of Windsor in Canada. This groundbreaking research focuses on the discovery of inhibitors targeting the NS2B-NS3 protease of the Zika virus, offering a new avenue for antiviral treatments. The NS2B-NS3 protease plays a vital role in the replication and maturation of the Zika virus. By inhibiting this enzyme, it’s possible to halt the virus’s ability to multiply and spread, making it a prime target for antiviral drugs.

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 (GLS-5700). Its first round in June 2016 was the first test of a Zika vaccine on humans. In August 2016, the National Institutes of Health (NIH) in Bethesda, Maryland, initiated clinical testing for a DNA-based Zika vaccine known as VRC 705. As of now, this promising vaccine has advanced to Phase 2 clinical trials. Several other companies are conducting preclinical studies of Zika vaccines, including Takeda (Osaka, Japan), GlaxoSmithKline (Brentford, UK), and Sanofi (Paris, France).

CONCLUSION

The emergence of the Zika virus in the United States poses a significant public health crisis, marked by its neurological impact on both infants and adults. Despite expedited FDA approvals for diagnostic tests and ongoing research for treatments and vaccines, the absence of comprehensive legislative action remains a critical gap. The situation calls for urgent, coordinated efforts from medical professionals, policymakers, and the public to address this multifaceted challenge effectively. As we continue our journey in understanding and combating Zika, it’s imperative to stay informed, remain vigilant, and trust in the power of scientific progress to guide us toward a safer future

FREQUENTLY ASKED QUESTIONS

1. What are the primary modes of Zika virus transmission?

The Zika virus is predominantly transmitted through the bite of an infected mosquito. Additionally, sexual transmission has been confirmed, with the virus persisting in infected individuals for up to six months.

2. What neurological implications are associated with Zika infection?

The virus has been conclusively linked to microcephaly in infants, characterized by significantly reduced brain size. In adults, preliminary research suggests that Zika may subtly impact neural progenitor cells, potentially affecting cognitive functions such as learning and memory.

3. Are there FDA-approved diagnostic tests for Zika?

The FDA has granted Emergency Use Authorizations for a range of RNA-based and antibody-based diagnostic tests to expedite the identification of Zika infections.

4. Is there a cure or vaccine for the Zika virus available?

At present, no definitive cure or vaccine exists for Zika. Supportive treatments, including rest and hydration, are the current standard of care. Ongoing research aims to identify effective antiviral medications and vaccines.

5. What public health measures are being implemented to mitigate the spread of Zika?

While federal legislation remains pending, state-level initiatives and public awareness campaigns are being employed to control mosquito populations and educate the public on preventive measures.

6. What preventive actions can individuals undertake?

Preventive strategies include using mosquito repellents, wearing protective clothing, and implementing mosquito control measures indoors and outdoors. For those who are pregnant or considering pregnancy, specialized healthcare consultation is strongly advised.

Author: Emily Burke, PhD
Editor: Sarah Van Tiems, MS
Scientific Review: Tahir Hayat, MS

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