Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

First steps to neutralizing Zika

24.11.2016

How highly potent antibody neutralizes Zika infection discovered

As Zika spreads throughout the world, the call for rapid development of therapeutics to treat Zika rings loud and clear. Taking a step further in identifying a possible therapeutic candidate, a team of researchers at Duke-NUS Medical School (Duke-NUS), in collaboration with scientists from the University of North Carolina, have discovered the mechanism by which C10, a human antibody previously identified to react with the Dengue virus, prevents Zika infection at a cellular level.


C10 antibody (purple) visualized to be interacting with the Zika virus coat (green).

Credit: Victor Kostyuchenko, Duke-NUS Medical School

Previously, C10 was identified as one of the most potent antibodies able to neutralise Zika infection. Now, Associate Prof Lok Shee-Mei and her team at the Emerging Infectious Disease Programme of Duke-NUS have taken it one step further by determining how C10 is able to prevent Zika infection.

To infect a cell, virus particles usually undergo two main steps, docking and fusion, which are also common targets for disruption when developing viral therapeutics. During docking, the virus particle identifies specific sites on the cell and binds to them. With Zika infection, docking then initiates the cell to take the virus in via an endosome - a separate compartment within the cell body. Proteins within the virus coat undergo structural changes to fuse with the membrane of the endosome, thereby releasing the virus genome into the cell, and completing the fusion step of infection.

Using a method called cryoelectron microscopy, which allows for the visualisation of extremely small particles and their interactions, the team visualised C10 interacting with the Zika virus under different pHs, so as to mimic the different environments both the antibody and virus will find themselves in throughout infection. They showed that C10 binds to the main protein that makes up the Zika virus coat, regardless of pH, and locks these proteins into place, preventing the structural changes required for the fusion step of infection. Without fusion of the virus to the endosome, viral DNA is prevented from entering the cell, and infection is thwarted.

"Hopefully, these results will further accelerate the development of C10 as a Zika therapy to combat its effects of microcephaly and Guillain-Barré syndrome. This should emphasise the need for further studies of the effect of C10 on Zika infection in animal models," commented Dr Lok.

"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," says Ralph Baric, PhD, professor in the Department of Epidemiology at UNC's Gillings School of Global Public Health.

These findings suggest that C10 may be developed as a therapy for Zika infection, and should be further explored. In addition, disrupting fusion with C10 may prove to be more effective in preventing Zika infection compared with therapies that attempt to disrupt docking. This is because the fusion step is critical for Zika infection, while the virus may develop other mechanisms to overcome disruptions to the docking step. With the call for rapid development of Zika therapies, C10 has emerged as a front runner to answer this call.

Published on 24 November 2016 in Nature Communications, this research is supported by the Singapore Ministry of Education Tier 3 Grant (MOE2012-T3-1-008), the National Research Foundation Investigatorship Award (NRF-NRFI2016-01 to Lok Shee-Mei), Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore, and National Institute of Health (USA) AID Research Grants (AI100625, AI107731 to Ralph S. Baric).

Yen May Ong | EurekAlert!

Further reports about: Zika infection Zika virus Zika virus coat structural changes

More articles from Health and Medicine:

nachricht Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

A paper battery powered by bacteria

21.08.2018 | Power and Electrical Engineering

Protein interaction helps Yersinia cause disease

21.08.2018 | Life Sciences

Biosensor allows real-time oxygen monitoring for 'organs-on-a-chip'

21.08.2018 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>