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New study highlights importance of targeting unchanging parts of COVID-19 virus
![Corewell Health COVID-19 sequencing data. (A) Sequencing statistics for samples analyzed at Corewell Health using Illumina chemistry. (B) SARS-CoV-2 genotypes per month from December 2021 through December 2023. The “*” indicates months with further processing in panel D. (C) Correlation analysis of the Pangolin annotation each month from the USA (with While vaccines target the changing parts of coronavirus, we must also pay attention to the unchanging parts](https://scx1.b-cdn.net/csz/news/800a/2024/while-vaccines-target.jpg)
For the past three years, Corewell Health researchers have been studying the genetic code of the virus that causes COVID-19 to better understand how it is changing and how to avoid another pandemic. Much of the world's focus has been on the development of vaccines to prevent the spread of the virus; however, vaccines primarily target the portion of the virus that constantly changes, requiring vaccines to be regularly updated
The new research, published in the journal Microorganisms, highlights that it is the unchanging parts of the virus that may provide reliable targets for new treatment strategies.
The key findings of the study, which evaluated COVID-19 samples from western areas of Michigan, were:
- Most of the critical parts of the virus that causes COVID-19 have stayed the same throughout the entire pandemic.
- The spike protein is a component of the virus that is used to get into human cells; however, it has constantly changed throughout the pandemic. Vaccines have been the mainstay of combating coronavirus by reducing transmission and severity of infection; yet because vaccines only target the spike protein, many studies neglect discussing the unchanging parts of the virus.
- Small molecule drugs, including antivirals that target parts of the virus that do not change, such as the enzymes that allow the virus to replicate, can provide effective treatment strategies in future outbreaks and play a key role in complementing vaccination strategies.
- Surveillance efforts are critical for understanding which parts of the virus change over time, how quickly those changes occur, and how consistently the virus changes in various parts of the world to inform public health efforts and development of treatments.
"Over the past few years, our study genotyped thousands of COVID-19 samples," said Adam Caulfield, Ph.D., director of the microbiology lab at Corewell Health in Grand Rapids, Michigan, and co-principal investigator of the study.
"In addition to detailing which parts of the virus are most susceptible to changes, it was amazing how closely the changes we were seeing in west Michigan correlated with what was happening elsewhere in the country. Our findings showed the value of surveillance for public health initiatives, while identifying stable parts of the virus as potential candidates for small molecule drugs and other drug development."
Small molecule drugs typically are the everyday drugs we take to cure headaches, allergies, and in the case of COVID-19, fight harmful viruses.
"It's the small molecule drugs such as nirmatrelvir, also known as Paxlovid, on the market today that continue to work as well as ever," said Jeremy Prokop, Ph.D., data science advisor at Corewell Health, who also led the study.
"While vaccines are important and target the changing parts of the virus, the perception exists that other drugs need to change as well and that is simply not the case. Based on our data, it is the small molecule drugs that are the consistent and reliable treatment factor related to COVID-19, and we need to keep advancing these drugs to learn more about how we can better manage another pandemic."
Prokop added that now that the country is experiencing another wave of COVID-19 infections, people need to be reassured that these small molecule drugs continue to work.
The new study is the deepest exploration to date using genotyping to understand the structure of proteins in the virus that causes COVID-19. Genotyping is the method used to investigate genetic strains of organisms. Over the past few years, federal agencies such as the Centers for Disease Control and Prevention (CDC), have supported the use of genotyping to investigate COVID-19. Yet now that it is past the pandemic stage, work in this area has been scaled back and centralized.
"Unlike the majority of genotyping programs that focus on ribonucleic acid (RNA), or protein changes to spike, we are showing the incredible number of known consistent structures where there may be small molecule drugs that can target the biology of a virus like SARS-CoV-2 and will continue to be stable as targets," Prokop said. "It's these targets that will help drive further drug development and provide even more solid treatment options for future outbreaks."
Corewell Health, along with other state and federal health agencies, continues to focus on staying one step ahead of COVID-19 and making sure there's ongoing tracking of the virus.
"We need to keep asking ourselves, "At what point does part of this virus change so much that it may find a different way to adhere to other immune cell receptors, and then open up the possibility for a whole new pandemic,'" Prokop said. "Maintaining our focus on small molecule drugs and treatments as well as understanding how the virus is changing in our local communities allows us to better care for everyone that has or will get the virus."
Additional researchers from Corewell Health also contributed to the study, as well as institutions including Michigan State University College of Human Medicine, Oakland University William Beaumont School of Medicine and Walsh University.
More information: Jeremy W. Prokop et al, SARS-CoV-2 Genotyping Highlights the Challenges in Spike Protein Drift Independent of Other Essential Proteins, Microorganisms (2024). DOI: 10.3390/microorganisms12091863