Tracking the evolution of SARS-CoV-2 viral mutations-ScienceDaily

A group of graduate students in the Spring Semester Bioinformatics and Systems Biology class in Illinois started with the first SARS-CoV-2 genome to determine the mutation rate of the viral proteome (a collection of proteins encoded by genetic material). Tracked over time. Published in January, more than 15,300 genomes will be terminated in late May.

The team found that some regions were still actively spinning off new mutations. This shows continuous adaptation to the host environment. However, mutation rates in other regions merged around a single version of the major protein and showed signs of slowdown.

“That’s bad news. The virus is changing and changing, but it keeps what is most useful or interesting to itself,” said a professor of bioinformatics at the Illinois Department of Crop Science.

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

Tre Tomaszewski, Ph.D. student and lead author of the Illinois Faculty of Information Science, said: “For example, in vaccine development, we need to know what the antibody is attached to. New mutations can change everything, including how the protein is built, their shape. The antibody target is the surface of the protein. It can fold inside from and cannot be reached any further. Knowing which proteins and structures are attached provides important insights into vaccines and other therapies.

The research team recorded a general slowdown in viral mutation rates beginning in April after an initial period of rapid change. This included stabilization within the spike protein, which gives the coronavirus a coronary appearance.

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

“Spike was a completely different protein at first, and now we can hardly find its first version,” says Tomaszewski.

Spike proteins, organized in two major domains, attach to human cells and help inject and replicate RNA, the genetic material of the virus. The 614 mutation breaks important bonds between different domains and protein subunits within the spike.

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

The 614 mutation was associated with increased viral load and increased infectivity in previous studies and did not affect the severity of the disease. However, in another study, mutations were associated with higher mortality. Although its role in pathogenicity needs to be confirmed, Tomaszewski says mutations clearly mediate invasion of host cells and are therefore important for understanding the transmission and spread of the virus.

Notably, sites within the other two notable proteins, including the NSP12 polymerase protein that replicates RNA and the NSP13 helicase protein that calibrates the replicated RNA strand, have also become more stable since April.

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

Researchers also noted that the area of ​​the viral proteome became more variable over time. Specifically, increased mutations in the nucleocapsid protein, which packages viral RNA after entering the host cell, and the 3a biloporin protein, which forms pores in the host cell to promote viral release, replication, and toxicity. I found that I was doing it.

These are areas of interest, as the researchers suggest that the increased non-random variability of these proteins suggests that the virus is actively seeking ways to improve its spread. Stated. Caetano-Anolles explains that these two proteins interfere with the way our body fights the virus. They are the major blockers of the beta interferon pathway that make up antiviral defense. Those mutations may explain the uncontrolled immune response that causes so many COVID-19 deaths.

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