More than 77,000 people have been infected with monkeypox in more than 100 countries around the world. Like COVID-19, changes have made the virus stronger and more intelligent, allowing it to evade antiviral medications and vaccinations and spread to more people.
At the University of Missouri, a group of researchers has now pinpointed the precise changes in the monkeypox virus that support its ongoing infectiousness. The findings could result in a number of different things, including the development of new drugs that take into account the current mutations to increase their efficacy at reducing symptoms and the spread of the virus or modified versions of currently available drugs used to treat people with monkeypox.
Kamlendra Singh, a professor at the University of Missouri College of Veterinary Medicine and the director of the Christopher S. Bond Life Sciences Center, worked with Shrikesh Sachdev, Shree Lekha Kandasamy, and Saathvik Kannan, a student at Hickman High School, to examine the DNA sequences of more than 200 monkeypox virus strains that span several decades, from 1965, when the virus first began spreading, to outbreaks in the early 2000s and once more in 2022.
A crucial discovery was that the virus is currently accumulating mutations, particularly where medications and antibodies from vaccines are expected to interact, according to Sachdev. “By undertaking a temporal study, we were able to show how the virus has developed over time,” he added. Therefore, as the virus becomes more intelligent, it can resist being killed by medications or immune system antibodies and spread to additional people.
Needles in a haystack
Singh has spent close to 30 years researching virology and DNA genome replication. He said that the monkeypox virus’ homology, or structural similarity, to the vaccinia virus, which has been utilized as a smallpox vaccine, is striking. As a result, Singh and his team were able to develop a precise 3D computer model of the monkeypox viral proteins and pinpoint the locations of specific mutations, as well as the roles they played in the virus’s recent rise in infectiousness.
Monkeypox is a massive virus with over 200,000 DNA bases in its genome, and our focus is on looking at the specific genes involved in copying the virus genome, according to Singh. “The almost 200 proteins that make up the monkeypox genome provide it all the “armor” it needs to reproduce, split, and spread to other people.” “Only the most adaptable viruses will survive because they produce billions of copies of themselves, which helps them adapt and propagate.”
When examining the various monkeypox virus strains, Kannan and Kandasamy focused on five distinct proteins: DNA polymerase, DNA helicase, bridging protein A22R, DNA glycosylase, and G9R.
When they forwarded the data to me, I could see that the mutations were happening at crucial locations that affected DNA genome binding and where medications and vaccine-induced antibodies are expected to bind, according to Singh. “These elements undoubtedly have a role in the virus’s heightened infectiousness. This job is crucial since it requires a collaborative effort and is the first step in solving a problem: pinpointing the location where the issue is actually occurring.
The evolution of viruses
The evolution of the monkeypox virus over time is still a topic of debate among scientists. Because the medications were first created to treat HIV and herpes but later acquired emergency use authorization in an effort to stop the latest monkeypox outbreak, their effectiveness in treating monkeypox has been below average.
According to Singh, the monkeypox virus may have become more intelligent and altered itself to avoid the medications when individuals were unknowingly infected with HIV and herpes while receiving treatment for both conditions with these drugs. Another theory is that the monkeypox virus may use proteins found in our bodies to become more dangerous and contagious.
Since the COVID-19 pandemic started in 2020, Singh and Kannan have worked together to pinpoint the precise mutations that cause COVID-19 variations like Delta and Omicron. The United Nations recently honored Kannan for his support of their “Sustainable Development Goals,” which aid in overcoming the biggest problems facing the planet.
“It is satisfying to be a part of it,” Singh said. “I could not have done this research without my team members, and our efforts have helped scientists and drug developers assist with these virus outbreaks.”
The Journal of Autoimmunity just released an article titled “Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak.” Shrikesh Sachdev, Athreya Reddy, Shree Lekha Kandasamy, Siddappa Byrareddy, Saathvik Kannan, and Christian Lorson are co-authors of the paper.
