New weapons
against emerging viruses

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VIZIER
When a new virus appears on the scene, it takes a long time to develop the drugs needed to stop it in its tracks. Now the VIZIER (‘Comparative structural genomics of viral enzymes involved in replication’) project is ensuring that in the future, scientists will be able to react rapidly and develop new drugs against a major class of viruses within weeks.

The project has already made important breakthroughs. New viruses carried by ticks and rodents have been identified, and findings made within VIZIER have been taken up by pharmaceutical companies developing drugs to treat Dengue Fever and Respiratory Syncitial Virus.

VIZIER is the world’s largest structural genomics project to date, bringing together 23 partners from 9 EU Member States, plus Russia. The team brings together scientists from virology, protein work, biochemistry, crystallography and drug design, among other fields.

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Waking up to the threat

The relative absence of deadly viruses in Europe has lulled many of us into a false sense of security about the threats to our health. But when the world was hit by Avian Influenza and Severe Acute Respiratory Syndrome (SARS) outbreaks in recent years, it became more apparent than ever that Europe is not immune to the threats of new and lethal viruses. Meanwhile, known viruses continue to claim the lives of millions of people in less developed parts of the world.

The VIZIER project is focusing its efforts on RNA viruses, so named because of the ribonucleic acid in their genetic material. Over 350 RNA viruses which can infect humans have been identified, including gastroenteritis, measles, influenza, yellow fever and hepatitis C. Together they are the cause of millions of deaths every year, yet our knowledge of their genetic make up and structures is relatively poor.

The aim of VIZIER is to investigate over 300 of these viruses in depth with the aim of identifying new drug targets. The team’s research takes place in five stages: collecting viruses, sequencing them, protein production, crystallisation and the initial steps of drug discovery and design.

A step-by-step approach to understanding viruses

The research begins with the collection of viruses from around the world. When the project began, many of these viruses were already stored in some of the project partners’ laboratories. But others had to be collected. In doing so, the project has created a series of biodiverse libraries that should help scientists to deal with any future virus outbreaks.

Once they have been collected, the genome of the virus is sequenced. Sequencing allows scientists to see what is involved in the replication of each individual virus and also create a three-dimensional model of the protein produced by the virus.

Using bacteria to farm proteins

The next stage of the project involves investigating the proteins involved in virus replication. The gene for the protein is injected into a bacterium, which is used as a factory to create the protein. While this works for some proteins, others have to be grown in a cell closer to that in which it would normally live. High-tech labs in France and the UK are being used for this part of VIZIER.

The next stage – crystallisation – is where VIZIER has had many of its breakthroughs. Indeed, the success of the project depended upon crystallisation of proteins, as crystals are essential for determining the molecular form of the protein that spreads a virus and thus for developing drugs. Results here have exceeded expectations, according to project coordinator Bruno Canard from the Université de la Méditerranée in France. Over 70 new crystal structures of original viruses within the RNA virus family have already been created.

VIZIER clears obstacles to crystal creation

Previous projects have had only limited success with creating crystals. Dr Canard believes that VIZIER succeeded where others experienced difficulties because of the multidisciplinary nature of the project and the exceptional communication between the partners.

The high-throughput methods used by the project also proved to be groundbreaking. Creating crystals is often the bottleneck of this type of research. The previously laborious process involved one scientist working solely on one protein. Discoveries could take years. VIZIER’s high-throughput methods, involving robotics, are what made the creation of so many crystals possible.

Once the crystals are formed, they are put into a synchrotron. The ring of the synchrotron carries electrons travelling close to the speed of light. They produce an intense source of X-rays that can be used to illuminate the molecular form of the proteins within. Knowledge of this molecular form can help scientists to design a compound that will stop the virus from replicating.

Preparing for future epidemics

Knowing that one virus is similar in structure to another provides clues as to which compounds might work. When SARS emerged in 2002, previous work on related viruses meant that a potential drug was developed within weeks of the virus being identified. The epidemic claimed 774 lives, but this number could have been devastatingly higher. The VIZIER project was set up in the aftermath of this crisis, with the aim of ensuring that reaction times will be equally fast if and when a new virus emerges. All findings will be stored in databases that can be accessed by the scientific community.

We don’t know where the next deadly virus will come from, or when it will strike, but thanks to projects like VIZIER, we will be better equipped to respond to it before it turns into a full-blown epidemic.