Monkeypox has infected more than 77,000 people in more than 100 countries around the world, and mutations – similar to COVID-19 – have enabled the virus to grow stronger and smarter, avoiding antiviral drugs and vaccines on its mission to infect more people.
Now, a team of researchers at University of Missouri identified mutations in monkeypox virus that contribute to persistent infection. the findings It could lead to several outcomes: modified versions of existing drugs used to treat people with monkeypox or the development of new drugs responsible for existing mutations to increase their effectiveness in reducing symptoms and the spread of the virus.
Kamlendra Singh, a professor in the MU College of Veterinary Medicine and principal investigator at the Christopher S. Bond Center for the Life Sciences, teamed up with Shrikesh Sachdev, Shree Lekha Kandasamy and Hickman High School student Saathvik Kannan, to analyze the DNA sequences of more than 200 strains of monkeypox. The virus spanned many decades, From 1965, when the virus first began spreading, to outbreaks in the early 2000s and again in 2022.
“By doing a chronological analysis, we were able to see how the virus has evolved over time, and the main finding was that the virus is now accumulating mutations precisely where drugs and antibodies from vaccines are supposed to bind,” Sachdev said. “So the virus is getting smarter, it is able to avoid being targeted by drugs or antibodies from our body’s immune response and continue to spread to more people.”
Needles in a haystack
Singh has been studying virology and DNA genome replication for nearly 30 years. The homology, or structure, of the monkeypox virus is very similar to the vaccinia virus, which was used as a smallpox vaccine, he said. This enabled Singh and his collaborators to create an accurate 3D computer model of monkeypox virus proteins and to determine where the specific mutations were and what their functions were in contributing to the virus becoming so infectious recently.
Subscribe to Outbreak News TV on YouTube
“Our focus is to look at the specific genes involved in transcribing the virus’ genome, and monkeypox is a massive virus with approximately 200,000 DNA bases in the genome,” Singh said. “The monkeypox DNA genome is transcribed into roughly 200 proteins, so it comes with all the ‘shields’ it needs to multiply, divide and continue to infect others. Viruses will make billions of copies of themselves, and only the fittest will survive, as Mutations help them adapt and continue to spread.”
Kannan and Kandasamy examined five specific proteins while analyzing monkeypox virus strains: DNA polymerase, DNA hellase, bridging protein A22R, DNA glycosylase and G9R.
“When they sent me the data, I saw that mutations occur at critical points that affect DNA-genome binding, as well as where vaccine-induced drugs and antibodies are supposed to bind,” Singh said. These factors certainly contribute to the increased infection of the virus. This work is important because the first step toward solving a problem is to identify precisely where the problem occurred in the first place, and it is a team effort.”
Save on ASUS Laptops and Desktops
Virus evolution
Researchers continue to question how the monkeypox virus evolved over time. The effectiveness of current CDC-approved drugs for treating monkeypox was suboptimal, likely because they were originally developed to treat HIV and herpes, but have since obtained emergency use authorization in an effort to control monkeypox outbreaks. the last one.
“One hypothesis is that when patients for HIV and herpes are treated with these drugs, they may also have contracted monkeypox without their knowledge, and the monkeypox virus became more intelligent and mutated to avoid the drugs,” Singh said. “Another hypothesis is that the monkeypox virus may hijack the proteins in our bodies and use them to become more infectious and pathogenic.”
Singh and Kanan have been collaborating since the COVID-19 pandemic began in 2020, to identify the specific mutations that cause COVID-19 variants, including Delta and Omicron. Kinan was recently honored by the United Nations for its support of the Sustainable Development Goals, which help address the world’s biggest challenges.
“I couldn’t have done this research without my team members, and our efforts have helped scientists and drug developers help with the outbreak of these viruses, so it’s rewarding to be a part of it,” Singh said.
