Researchers have identified specific mutations in the monkeypox virus that have made it "smart" enough to avoid being targeted by medicines or a body's immune response and continue being contagious.

The findings of the study, published in the Journal of Autoimmunity, can help in modifying existing drugs used to treat monkeypox or developing new medicines that can counter the mutations thus reducing symptoms of the disease and curbing the spread of the virus.

The study was conducted by a team of researchers at the University of Missouri. "By doing a temporal analysis, we were able to see how the virus has evolved over time. A key finding was that the virus is now accumulating mutations specifically where drugs and antibodies from vaccines are supposed to bind," researcher Shrikesh 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," he added.

Kamlendra Singh, a professor in the MU College of Veterinary Medicine and Christopher S. Bond Life Sciences Center principal investigator, collaborated with Shrikesh Sachdev, Shree Lekha Kandasamy, and Hickman High School student Saathvik Kannan in the study.

For the study, the team analysed the DNA sequences of more than 200 strains of the monkeypox virus spanning multiple decades, from 1965 when it first started spreading, to outbreaks in the early 2000s and most recently in 2022.

"Our focus is on looking at the specific genes involved in copying the virus genome. Monkeypox is a huge virus with approximately 200,000 DNA bases in the genome," lead researcher Kamlendra Singh said.

"The DNA genome for monkeypox is converted into nearly 200 proteins. So, it comes with all the 'armour' it needs to replicate, divide and continue to infect others."

"Viruses will make billions of copies of themselves and only the fittest will survive as the mutations help them adapt and continue to spread," Singh said.

Kannan and Kandasamy examined five specific proteins while analysing the monkeypox virus strains. These were DNA polymerase, DNA helicase, bridging protein A22R, DNA glycosylase, and G9R.

"When they sent me the data, I saw that the mutations were occurring at critical points impacting DNA genome binding, as well as where drugs and vaccine-induced antibodies are supposed to bind," Singh said.

"These factors are surely contributing to the virus's increased infectivity. This work is important because the first step toward solving a problem is identifying where the problem is specifically occurring. It is a team effort," he said.

Researchers continue to question how the monkeypox virus has evolved over time.

The efficacy of current Centres for Disease Control and Prevention (CDC)-approved drugs to treat monkeypox have been suboptimal, likely because they were originally developed to treat HIV and herpes but have since received emergency use authorisation in an attempt to control the recent monkeypox outbreak.

"One hypothesis is when patients were being treated for HIV and herpes with these drugs, they may have also been infected with monkeypox without knowing. The monkeypox virus got smarter and mutated to evade the drugs," Singh said.

"Another hypothesis is the monkeypox virus may be hijacking proteins we have in our bodies and using them to become more infectious and pathogenic." Singh and Kannan have been collaborating since the onset of the COVID-19 pandemic, identifying specific mutation-causing coronavirus variants, including Delta and Omicron.

Monkeypox has infected more than 77,000 people in more than 100 countries. Just as in the case of COVID-19, in monkeypox too, mutations have enabled the virus to grow stronger and smarter, evading anti-viral drugs and vaccines and infecting more people.