By Nishtha Rampuria
The recent Zika epidemic lasting from 2015-16 in Africa, Southeast Asia, and the Pacific has left the entire world in a shock. In January 2016 the WHO released a statement that the Zika virus is most likely to spread all across Americas by 2016. This statement put scientists and people across the world especially, the Americas in a panic state and called for an immediate cure for this virus. A team of researchers at Duke-NUS Medical School along with researchers from the University of North Carolina discovered an important key to finding the antidote for Zika virus - how antibodies can neutralize Zika. This pioneering research could be extremely prudent in resolving the issue of Zika and could help the situations of the Americas in terms of eliminating the disease.
What do we know about Zika? Zika is caused and spread by an infected Aedes mosquito. The recent outbreak has triggered a worry for especially pregnant women affected by Zika. The WHO website states the following conclusion that has put everyone in worry “WHO has concluded that Zika virus infection during pregnancy is a cause of congenital brain abnormalities, including microcephaly - a disease that causes the affected (usually infants) to have a small head and failed/major difficulty in growth; Zika virus is a trigger of Guillain-Barré syndrome”. Brain abnormalities especially the Guillain-Barre syndrome can cause paralysis or even death. As a response, the WHO has created a “Zika Strategic Response Plan” lasting from July 2016 to December 2017 that outlines the following steps: Detection, Prevention, Care and Support, Research and Coordination. The published research is particularly aimed to find preventive medicines for this disease.
Through a joint venture, researchers at DUKE-NUS university and North Carolina University discovered that C10 (human antibody) can prevent the Zika infection. In fact, C10 has previously been proven as one of “the most potent antibodies”, which led assistant Prof. Shee-Mei Lok, Ph.D. at Duke-NUS Emerging Infection Disease Program and Prof Ralph Baric, Ph.D., professor of epidemiology at UNC’s Gillings School of Global Public health with their team to research if C10 could be a vaccine for Zika virus.
“By defining the structural basis for neutralization, these studies provide further support for the idea that this antibody will protect against Zika infection, potentially leading to a new therapy to treat this dreaded disease,” said Prof Ralph Baric.
In order to infect the cell, the researchers went through the process of docking and fusion. These processes play a key role in targeting a particular cell for creating “viral therapeutics”. In the process of docking, the virus locates particular sites on the cell and then attaches to them. With this infection, docking then begins the cells to take in the virus through an endosome. Proteins in the virus coat go through changes in its structure in order to fuse with the endosome’s membrane, after which it releases the virus genome into the cell. This terminates the fusion part of the virus.
Using an experimental technique known as “cryo electron microscopy” the researchers saw C10 interacting with the virus at various pH levels. Cryo electron microscopy is an imaging technique. It is a form of well-known transmission electron microscopy and enables to see detailed images of frozen samples at a molecular level. In this method, an electron gun shoots electrons at the speed of light wherein they pass by the sample. Then a camera through which the electrons pass, capture and form the image of the sample. The images formed are not always still. The camera has a feature wherein moving images can too be captured and displayed. It was tested at different pH levels to predict how in various environments C10 and the virus will find themselves in all through the infection. It was found that the antibody C10 binds to the main proteins that make the Zika virus’s coat. This leads to locking of these proteins into place hence blocking the structural changes that are required for the fusion step to occur despite the different pH levels. The viral DNA is stopped from entering the cell because the fusion of the virus to the endosome did not occur hence the infection is neutralized.
“Hopefully, these results will further accelerate the development of C10 as a Zika therapy to combat its effects of microcephaly and Guillain-Barré syndrome,” Prof Shee-Mei Lok said. “This should emphasize the need for further studies of the effect of C10 on Zika infection in animal models.”
This research has successfully been able to suggest and prove that C10 can be developed as a therapy for Zika virus. Additionally, the research has been able to disrupt the process of fusion with C10 without disturbing docking that may prove that this therapy may be more effective in regards to preventing Zika virus. “With the urgent need for rapid development of Zika therapies, C10 has emerged as a front-runner to answer the call.” -UNC Gillings School of Global and Public Health
Zhang S, et al. Neutralization mechanism of a highly potent antibody against Zika virus. Nat. Commun. 7, 13679 doi: 10.1038/ncomms13679 (2016).
UNC Gillings School of Global Public Health. “UNC, Duke-NUS team identifies first step to neutralizing Zika." UNC, Duke-NUS team identifies first step to neutralizing Zika ||. November 28, 2016. http://sph.unc.edu/sph-news/unc-duke-nus-team-find-first-steps-to-neutralizing-zika/.
Various Authors. "2015–16 Zika virus epidemic." Wikipedia. Accessed January 08, 2017. https://en.wikipedia.org/wiki/2015%E2%80%9316_Zika_virus_epidemic.
World Health Organization. "Zika virus and potential complications." Accessed January 08, 2017. http://www.who.int/features/qa/zika/en/.
Duke-NUS Medical School. "First steps to neutralising Zika. 28th November 2016. Accessed January 08, 2017. https://www.duke-nus.edu.sg/news/first-steps-neutralising-zika.
Bruce B. Vanderburg “How C10 antibodies neutralize Zika” Accessed January 08, 2017. http://reliawire.com/c10-neutralizes-zika/
About the Author
Nishtha Rampuria is currently a freshman in Pathways World School. Her interest in science has indeed been short term yet very wide and vivid. She has a special inclination towards in neurobiology, genetics and astrobiology. She has also been a keen writer across her years in middle school. She is currently working on creating a study module for schools in order to improve the level of understanding of healthcare and first aid education. Apart from writing and science she takes an avid interest in Model UNs, debating and reading.
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