There is currently no vaccine or medicine against Zika – a mosquito-borne virus that causes birth defects and, in its recent outbreak, has infected more than 1 million people in the Americas and Caribbean. Now, by mapping a protein that helps the Zika virus to replicate and spread, researchers take a significant step toward a cure.

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The researchers mapped the structure of the Zika virus protein NS5, which helps the virus to replicate and spread.
Image credit: Cheng Kao, Indiana University

A study focusing on mapping the protein structure – led by Indiana University (IU) in Bloomington in collaboration with Texas A&M University in College Station – is published in the journal Nature Communications.

Although most commonly spread through bites from Aedes mosquitoes, Zika virus can also spread through sexual activity. Symptoms of infection last for 2 to 7 days and include mild fever, a skin rash, eye inflammation (conjunctivitis), headache, and muscle and joint pain.

The symptoms of Zika virus infection are often so mild that people barely notice them.

Zika virus belongs to the genus Flavivirus, which includes viruses that cause yellow fever, West Nile virus, dengue fever, Japanese encephalitis, hepatitis C, and other significant diseases in humans. It was first identified in monkeys in Uganda in 1947.

Scientists now agree that Zika virus can cause microcephaly in babies born to women infected during pregnancy. They also agree that it causes Guillain-Barré syndrome, a rare and serious autoimmune disorder.

In the recent outbreak, Zika virus has spread through the Americas, with more than 1 million cases reported in the latest World Health Organization (WHO) and Pan American Health Organization update. These include cases of local, mosquito-borne Zika virus spread in Texas and Florida in the continental United States.

At present, there is no vaccine or medication against Zika infection, so currently the best way to prevent infection is by avoiding mosquito bites and practicing safe sex.

Cheng Kao, a professor in the Department of Molecular and Cellular Biology at IU and one of the senior investigators on the new study, says:

“We need to do everything we can to find effective drugs against the Zika virus, as changes in travel and climate have caused more tropical diseases to move into new parts of the globe.”

Prof. Kao has spent the past 15 years studying the virus that causes hepatitis C virus and has also worked on HIV, the virus that causes AIDS. He says that this experience has helped to increase understanding about how to fight Zika.

In their new paper, Prof. Kao and his colleagues report how they mapped an important protein in the Zika virus – called nonstructural protein 5 (NS5) – that helps it to replicate and spread.

NS5 contains two enzymes: one that reduces the body’s immune response, and another that triggers the replication of the Zika virus.

The researchers determined the crystal structure of NS5 and also of sections relevant to the enzymes.

The study also found that the structure of Zika’s NS5 bears some “striking similarities to the NS5 protein of the related Japanese encephalitis virus.” They also found additional similarities with proteins from other flaviviruses.

The technology used to map the protein structure is currently the subject of a patent application.

Prof. Kao and his team are already working with industry partners to screen for compounds that target the NS5 protein in the Zika virus. They believe that drugs already approved to treat hepatitis C, and others in development to treat other flaviviruses, offer prime candidates for screening.

Mapping this protein provides us [with] the ability to reproduce a key part of the Zika virus in a lab. This means we can quickly analyze existing drugs and other compounds that can disrupt the spread of the virus. Drugs to target the Zika virus will almost certainly involve this protein.”

Prof. Cheng Kao

Learn about another powerful tool that should be useful for Zika vaccine and antiviral development.