Camouflage for the virus
A protein has been found that hides the coronavirus from immunity
American molecular biologists have discovered a protein mechanism that makes the RNA of a new type of coronavirus invisible to the innate immune system of those cells into which SARS-CoV-2 has already managed to penetrate. The results of their work were published by the scientific journal Nature Communications (Viswanathan et al., Structural basis of RNA cap modification by SARS-CoV-2).
"The virus produces the protein nsp16, which in a special way changes the structure of the end sections of copies of its genome. These changes play the role of camouflage, which deceives the cell and makes it consider the viral RNA part of itself, and not an alien inclusion," explained one of the authors of the study, associate professor at the University of Texas at San Antonio (USA) Yogesh Gupta.
Scientists believe that after infection with a new type of coronavirus (SARS-CoV-2), severe disorders develop in the work of the immune system. In addition, other problems arise – massive inflammation, microthrombs, which, even without COVID-19, threaten the patient's life. Now scientists are trying to understand why they appear and how to prevent them.
To answer this question, as Gupta notes, it is important to understand how the coronavirus penetrates human cells, bypasses the built-in protection system and how its appearance changes the vital activity of these cells. The first phase of this process is the "translation" of the virus genome into a "language" understandable to the cell.
To do this, each particle of the coronavirus has a set of auxiliary proteins that change the end sections of its RNA molecule in a special way, adding a short segment to them. Biologists call him "cap" (from the English. cap – cap).
This structure consists of a molecule of 7-methylguanosine – an analogue of one of the "letters" of RNA and DNA, it is present on all RNA copies of the genes of multicellular organisms. "Cap" serves as a label by which cells recognize their own and someone else's genetic material. If it is not there, the "stranger" is destroyed. Viruses try to counteract this by using their own tags or stealing them from the cell.
Gupta and his colleagues found out that in the case of coronavirus, the nsp16 protein solves this problem. Scientists found out its exact three-dimensional structure, and also studied the properties of the nsp10 enzyme, which plays an important role in the formation of the "cap" on copies of the SARS-CoV-2 genome. To do this, scientists obtained a large number of their molecules, combined them with 7-methylguanosine, then froze and enlightened them using an X-ray crystallograph.
Thanks to this, Gupta and colleagues understood exactly how this protein makes the coronavirus RNA molecules invisible to the immune system. In particular, they identified several critical areas of nsp16 and nsp10, the destabilization of which can disable this viral camouflage system.
Interestingly, the structure of nsp16 differs significantly in SARS-CoV-2, pathogens of atypical pneumonia, common colds and animal coronaviruses. How exactly the differences in their structure affect the work of the enzyme, scientists can not yet say for sure. However, their calculations show that they can increase its activity and expand the possible "repertoire" of molecules with which nsp16 can interact.
Further study of the vulnerabilities of nsp16 and nsp10, Gupta hopes, will lead to the creation of short molecules that can block their action and make the virus visible to the innate human immune system and other potential victims of COVID-19.
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