Mosquito protein analysis could lead to therapeutic treatment against deadly viruses

The mosquito protein AEG12 strongly inhibits the family of viruses that cause yellow fever, dengue, West Nile, and Zika and weakly inhibits coronaviruses, according to scientists at the National Institutes of Health (NIH) and their colleagues. The researchers found that AEG12 works by deregulating the viral envelope, breaking its protective coating. Although the protein does not affect non-enveloped viruses, such as those that cause pink eye and bladder infections, the findings could lead to antiviral treatment that affects millions of people. all over 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 crystals to unravel the structure of AEG12. Senior author Geoffrey Mueller, Ph.D., head of the NIEHS Nuclear Magnetic Resonance Group, said that at the molecular level, AEG12 breaks down the lipids, or fat-like sections of the membrane that holds the virus together.

“It’s as if AEG12 is hungry for the lipids that are in the membrane of the virus, so it gets rid of some of the lipids that are there and exchanges them for its favorites, Mueller said. “Protein has a high affinity for viral lipids and steals them from the virus.”

As a result, Mueller claims that the AEG12 protein has a great killing power over some viruses. Although the researchers showed that AEG12 was most effective against flaviviruses, the family of viruses to which Zika belongs, West Nile, and others, it is possible that AEG12 may be effective against SARS-CoV-2, the COVID-19-induced coronavirus. However, Mueller said it will take years of bioengineering to make AEG12 an operational treatment for COVID-19. Part of the problem with AEG12 is also the breakdown of opening red blood cells, so researchers need to identify fertilizers that make only the target viruses protein.

Alexander Foo, Ph.D., a NIEHS visitor and lead author of the paper, explained that mosquitoes produce AEG12 when they eat blood or get infected with flaviviruses. Like humans, mosquitoes react strongly to these viruses, with AEG12 exploding their viral cover. However, at the outset of the project, Foo and his colleagues had little knowledge of the work of AEG12.

“The prospect of exploring new proteins is exciting, but daunting,” said Foo. “Fortunately, we had enough knowledge and access to a wide range of knowledge at NIEHS to put it together.”

Co-author and crystal expert Lars Pedersen, Ph.D., is the director of the NIEHS Structure Action Group. He regularly uses information about molecular physical construction in his work and encourages more scientists to consider using this data in their learning. He said, “Our research shows that understanding protein structure can be important in figuring out what it does and how it can help with disease treatment. “

Source:

NIH / National Institute of Environmental Health Sciences

Magazine Reference:

Foo, ACY, et al. (2021) The mosquito protein AEG12 exhibits both cytolytic and antiviral properties through a common lipid transport mechanism. PNAS. doi.org/10.1073/pnas.2019251118.

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