Study tracks evolution of SARS-CoV-2 viral mutations

Since COVID-19 began a menacing march across Wuhan, China, and subsequently around the world in December 2019, the SARS-CoV-2 virus has “anything to ensure its replication and spread.” We have taken a “working” strategy. However, a new study undergoing peer review shows researchers and students at the University of Illinois are polishing the tactics that the virus can make more successful and more stable.

A group of graduate students in the spring semester bioinformatics and systems biology class in Illinois published the first published SARS-CoV-2 mutation rate for the viral proteome, a collection of proteins encoded by genetic material. Tracked starting from genome Ended with more than 15,300 genomes in January and late May.

Teams are still actively new in some areas mutation, Showing continuous adaptation to the host environment. However, mutation rates in other regions coalesced around a single version of the major protein and showed signs of slowing.

“That’s the bad news. The virus continues to change, but it maintains what is most useful or interesting in its own right,” says Gustavo Caetano-Anolles, professor of bioinformatics and senior author of the Illinois Department of Crop Science. He says. the study.

However, importantly, the stabilization of certain proteins may be good news for the treatment of COVID-19.

According to Tre Tomaszewski, first author of the PhD program at the School of Information Sciences in Illinois. “For example, in vaccine development, we need to know what the antibody is attached to. New mutations can change everything, including how proteins are constructed. Their shape. The antibody target is protein Once inside, I can’t get there anymore. Knowing which proteins and structures are well established provides important insights into vaccines and other treatments. “

Research team documented the overall slowdown of the virus Mutation rate It begins in April, after an initial period of rapid change. This includes stabilization within spike proteins, and pokey appendages that give the coronavirus a crowned appearance.

Within the spike, researchers found that the amino acid at site 614 was replaced with another amino acid (aspartic acid to glycine). This is a mutation that makes up the entire virus population in March and April.

“The spike was a completely different protein from the beginning and the present. The first version is almost undiscovered so far,” says Tomaszewski.

The spike protein, which is organized into two major domains, is Human cells RNA, the genetic material of the virus, is injected inside so that it can replicate. The 614 mutation disrupts critical binding between different domains within the spike and protein subunits.

“For some reason, this must help increase the spread and infectivity of the virus as it enters the host, otherwise the mutation will not be maintained,” says Caetano-Anolles.

In a previous study, the 614 mutation was associated with increased viral load and increased infectivity, and did not affect disease severity. However, in another study, mutations were associated with higher mortality. Tomaszewski states that its role in pathogenicity needs confirmation, but that mutations clearly mediate host cell entry and are therefore important for understanding viral transmission and spread.

Notably, the two other sites within the protein of interest were also more stable since April, including the NSP12 polymerase protein, which replicates RNA, and the NSP13 helicase protein, which calibrates the replicated RNA strand.

“All three mutations seem to work in concert with each other,” says Caetano-Anolles. “They are in different molecules, but they follow the same evolutionary process.”

The researchers also noted that the area of ​​the viral proteome was more susceptible to changes over time. It says that this could be an indication of what to expect next at COVID-19. Specifically, for nucleocapsid proteins that package viral RNA after entering the host cell and for mutations in the 3a viroporin protein that create pores in the host cell to facilitate virus release, replication, and pathogenicity. Found an increase.

According to the research team, these areas are notable areas. This is because the increased non-random variability of these proteins suggests that the virus is actively seeking ways to improve its spread. Caetano-Anolles explains that these two proteins interfere with the way our body fights the virus. They are the major inhibitors of the beta interferon pathway that make up our antiviral defenses. These mutations may explain the uncontrolled immune response responsible for the death of so many COVID-19s.

“Given this virus has been in the midst of us for some time, I hope that exploration of mutation pathways can predict moving targets for rapid treatment and vaccine development in preparation for the next wave.” “Tomazevsky said. “We will continue to track this virus with thousands of other researchers who sequence, upload, and curate genomic samples through the GISAID initiative.”

“A new pathway for mutational changes in the SARS-CoV-2 proteome involves a region of important intrinsic disorder Virus Replication and release” is published on the preprint server BioRxiv