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Treating Zika Infection: Repurposed Drugs Show Promise

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Zika researcher

Caption: An NCATS researcher dispenses Zika virus into trays for compound screening in a lab using procedures that follow strict biosafety standards.
Credit: National Center for Advancing Translational Sciences, NIH

In response to the health threat posed by the recent outbreak of Zika virus in Latin America and its recent spread to Puerto Rico and Florida, researchers have been working at a furious pace to learn more about the mosquito-borne virus. Considerable progress has been made in understanding how Zika might cause babies to be born with unusually small heads and other abnormalities and in developing vaccines that may guard against Zika infection.

Still, there remains an urgent need to find drugs that can be used to treat people already infected with the Zika virus. A team that includes scientists at NIH’s National Center for Advancing Translational Sciences (NCATS) now has some encouraging news on this front. By testing 6,000 FDA-approved drugs and experimental chemical compounds on Zika-infected human cells in the lab, they’ve shown that some existing drugs might be repurposed to fight Zika infection and prevent the virus from harming the developing brain [1]. While additional research is needed, the new findings suggest it may be possible to speed development and approval of new treatments for Zika infection.

Zika Vaccine: Two Candidates Show Promise in Mice

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Zika Virus

Caption: Zika virus (red), isolated from a microcephaly case in Brazil. The virus is associated with cellular membranes in the center.
Credit: NIAID

Last February, the World Health Organization declared a public health emergency over concerns about very serious birth defects in Brazil and their possible link to Zika virus. But even before then, concerns about the unprecedented spread of Zika virus in Brazil and elsewhere in Latin America had prompted NIH-funded scientists to step up their efforts to combat this emerging infectious disease threat. Over the last year, research aimed at understanding the mosquito-borne virus has progressed rapidly, and we now appear to be getting closer to a Zika vaccine.

In a recent study in the journal Nature, researchers found that a single dose of either of two experimental vaccines completely protected mice against a major viral strain responsible for the Zika outbreak in Brazil [1]. Caution is certainly warranted when extrapolating these (or any other) findings from mice to people. But, taking into account the fact that researchers have already developed safe and effective human vaccines for several related viruses, the new work represents a very encouraging milestone on the road toward a much-needed Zika vaccine for humans.

Snapshots of Life: Portrait of Zika Virus

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Cross section of the Zika virus

Credit: David Goodsell, The Scripps Research Institute

This lively interplay of shape and color is an artistic rendering of the Zika virus preparing to enter a cell (blue) by binding to its protein receptors (green). The spherical structures (pink) represent two Zika viruses in a blood vessel filled with blood plasma cells (tan). The virus in the middle in cross section shows viral envelope proteins (red) studding the outer surface, with membrane proteins (pink) embedded in a fatty layer of lipids (light purples). In the innermost circle, you can see the viral genome (yellow) coiled around capsid proteins (orange).

This image was sketched and hand-painted with watercolors by David Goodsell, a researcher and illustrator at The Scripps Research Institute, La Jolla, CA. Goodsell put paint and science to paper as part of the “Molecule of the Month” series run by RCSB Protein Data Bank (PDB), which NIH co-supports with the National Science Foundation and the Department of Energy. The PDB, which contains structural data on thousands of proteins and small molecules, uses its “Molecule of the Month” series to help students visualize a molecule or virus and to encourage their exploration of structural biology and its applications to medicine.

Snapshots of Life: Imperfect but Beautiful Intruder

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RSV Particle

Credit: Boon Chong Goh, Beckman Institute, University of Illinois at Urbana-Champaign

The striking image you see above is an example of what can happen when scientists combine something old with something new. In this case, a researcher took the Rous sarcoma virus (RSV)—a virus that’s been studied for more than century because of its ability to cause cancer in chickens and the insights it provided on human oncogenes [1, 2]—and used modern computational tools to generate a model of its atomic structure.

Here you see an immature RSV particle that’s just budded from an infected chicken cell and entered the avian bloodstream. A lattice of proteins (red) held together by short peptides (green) cover the outer shell of the immature virus, shielding other proteins (blue) that make up an inner shell.

AIDS Vaccine Research: Better By Design?

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OD-GT8 60mer

Caption: eOD-GT8 60mer nanoparticle based on the engineered protein eOD-GT8. Yellow shows where eOD-GT8 binds antibodies; white is the protein surface outside the binding site; light blue indicates the sugars attached to the protein; dark blue is the nanoparticle core to which eOD-GT8 has been fused.
Credit: Sergey Menis and William Schief, The Scripps Research Institute

A while ago, I highlighted a promising new approach for designing a vaccine against the human immunodeficiency virus (HIV), the cause of AIDS. This strategy would “take the immune system to school” and teach it a series of lessons using several vaccine injections—each consisting of a different HIV proteins designed to push the immune system, step by step, toward the production of protective antibodies capable of fending off virtually all HIV strains. But a big unanswered question was whether most people actually possess the specific type of precursor immune cells that that can be taught to produce antibodies that kill HIV.

Now, we may have the answer [1]. In a study published in the journal Science, a research team, partly supported by NIH, found that the majority of people do indeed have these precursor cells. While the total number of these cells in each person may be low, this may be all that’s needed for the immune system to recognize a vaccine. Based in part on these findings, researchers plan to launch a Phase 1 clinical trial in human volunteers to see if their latest engineered protein can find these precursor cells and begin coaxing them through the complicated process of producing protective antibodies.

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