Computer aided design of antiviral proteins may prevent the next pandemic

Bill gates believes that there are three main threats to our species: nuclear war, climate change and another global pandemic. Speaking at a conference in Munich devoted to pandemic preparedness, gates reminded us that "the fact that the global pandemic has not happened in recent history, should not be taken as a hint that its not going to happen in the future."

If we want to be prepared for the worst, says gates, "the first and most important thing we need to build an Arsenal of new weapons — vaccines, drugs and diagnostic tools."

Some scholars now use computers for this purpose.

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outside of the immune system

Despite the availability of flu vaccinations, the world health organization reports that seasonal flu is still responsible for millions of severe cases and about half a million deaths each year. Incomplete effectiveness of the annual flu vaccinations, along with a long production time and limited, said that new methods are needed to combat the flu.

And this is just seasonal flu. A flu pandemic like the Spanish flu of 1918 again could kill tens of millions of people in one year.

Antibodies are a natural part of the immune system, are at the front of the fight against viruses. The job of antibodies is to identify and physically eliminate the intruder like the flu. Human antibodies are bivalent, i.e., have two arms that can grab a goal.

Under the microscope the flu looks like a tiny ball with spikes. With the help of spikes on the surface it penetrates the human cell. Closely clinging to the thorns with one hand, antibodies can prevent the penetration of particles of influenza in cells. But every year the flu quickly acquires mutations in their protein spikes, which leads to the fact that the grasping hands of our antibodies do not recognize the virus.

Scientists have been searching for a universal flu vaccine — that will not have to recreate every year. As a rule, attempts to make it include the establishment of non-communicable doubles flus in the hope that they will prepare the immune system to attack, when the real strain of the flu attack. Despite some progress, scientists have been unable to force the immune system to protect against all strains of flu, and the threat of a global pandemic still remains.

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Software for the flu

Computer-aided design of proteins offers another way. Instead of relying on the immune system to generate proteins antibodies that can fight the virus, computer simulation can allow you to quickly create antiviral proteins that can destroy a deadly virus.

Unlike the vaccine, this class of drugs could be adapted to treat an existing infection or to prevent future. And since these designer proteins are independent of the immune system, their potential does not depend on the immune system — and this is useful for weak immune system, which are at high risk of infection.

Computer antiviral proteins work in the same way as the natural proteins in our immune system. Having surfaces that chemical complementary to the goals of antiviral proteins can closely cling to a specific virus. If the protein is correctly attached to the virus, it can physically block the movement of the virus, preventing infection.

Due to the development of antiviral protein on the computer you create it in the laboratory and the subsequent introduction into the body, it is possible to digitize part of the immune system.

In 2016, made on the computer the whites were better than oseltamivir in the rescue of mice from lethal infection. One dose of designer protein, administered internally, was more effective than 10 doses of Tamiflu, a drug that is considered "essential" according to the who for its anti-influenza action. Moreover, these computer antigrippoznye proteins protected the mice from the different strains of the flu. Attempts to hold these promising results through the FDA approval already under way.

In a recently published article in Nature Biotechnology, scientists from the Institute of protein design at the University of Washington went even further and demonstrated a new way to fight the flu: they used computer modelling to create an entirely new type antiviral protein with three prehensile hands.

Why three? It turns out that the shell of many deadly viruses — influenza, Ebola and HIV build the protein spikes of the three symmetrical parts.

One antiviral drug with three properly spaced hand must be able to capture every part of each protein spike, firmly bound him. This geometrical feat is beyond what he's capable of the human immune system.

Left: ends protein spikes of many viral proteins consist of three symmetrical parts, one highlighted in pink. Right: new three-handed anti-influenza protein (blue) binds to the spike of the influenza virus

Design Strategy worked. The best three-handed protein called Tri-HSB.1C could be closely contacted with various strains of influenza. When administered to mice it also gave complete protection against a lethal influenza virus due to a small weight loss. Now scientists are trying to use the same tools for Ebola.

It Will be many years before these technologies are approved for use on humans. However, it is possible to wait not so long.

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Viral diagnostics

Covered with a strip of paper three-handed wrestler with the flu, and put samples of the flu at the top, the same scientists were able to detect the presence of viral surface proteins even at very low concentrations. This proof of concept can turn into a reliable and accessible diagnostic tool for the field definitions of the different viruses in the saliva or blood. Like a pregnancy test, a strip of paper could identify the flu. Or Ebola. Or another rapidly spreading worldwide pandemic.

In the Epistle of 2015 in New England Journal of Medicine bill gates described the lack of preparation on the part of the world community as a "global failure."

"Perhaps the only good news after the tragic Ebola epidemic is that it will serve as a call to awakening".

If a global viral pandemic like the Spanish flu of 1918 was coming back, antiviral software can play an important role and save millions of lives.

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