Mosquito protein study could prompt therapeutics against dangerous viruses

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• Source: NIH/National Institute of Environmental Health Sciences


• Date: 11 Mar,2021

The researchers found that AEG12 works by destabilizing the viral envelope, breaking its protective covering. Although the protein doesn’t affect viruses that don’t have an envelope, such as the ones that cause pink eye and bladder ailments, the findings could lead to therapeutics against viruses which affect millions of people around the world. The research was published online in PNAS.

Scientists at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, used X-ray crystallography to solve the structure of AEG12. Senior author Geoffrey Mueller, Ph.D., head of the NIEHS Nuclear Magnetic Resonance Group, said at the molecular level, AEG12 rips out the lipids, or the fat-like parts of the membrane that hold the virus together.

As a result, Mueller says the AEG12 protein has great killing power over some viruses. While the researchers demonstrated that AEG12 was most effective against flaviviruses, the family of viruses to which Zika, West Nile, and others belong, it is likely AEG12 could be effective against SARS-CoV-2, the coronavirus that causes COVID-19. But, Mueller said it will take years of bioengineering to earn AEG12 a viable therapy for COVID-19. Part of the issue is AEG12 also breaks opens red blood cells, so researchers will need to identify substances that will make the protein target viruses only.

It is as if AEG12 is hungry for the lipids that are in the virus membrane, so it gets rid of some of the lipids it has and exchanges them for the ones it really prefers. The protein has high affinity for viral lipids and steals them from the virus.”

Geoffrey Mueller, Ph.D., Head, NIEHS Nuclear Magnetic Resonance Group

Alexander Foo, Ph.D., an NIEHS visiting fellow and lead author of the paper, explained that mosquitoes produce AEG12 when they take a blood meal or become infected with flaviviruses. Like humans, mosquitoes mount a vigorous immune response against these viruses, with AEG12 bursting their viral covering. But, at the start of the job, Foo and his colleagues understood little about the function of AEG12.

“The prospect of studying a new protein is exciting, yet daunting,” Foo said. “Happily, we had enough clues and accessibility to a wide range of experience at NIEHS to piece it together.”

Co-author and crystallography expert Lars Pedersen, Ph.D., is leader of the NIEHS Structure Function Group. He routinely uses information about a molecule’s physiological makeup in his job and encourages more scientists to consider using this data in their studies. He explained,”Our research shows that understanding the structure of a protein could be important in figuring out what it does and how it could help treat disease.”