As monkeypox cases increase, investigators are turning to smallpox antivirals.
As of last night, the US Centers for Disease Control and Prevention (CDC) reported there are 14511 confirmed cases of monkeypox, 14268 in countries that have not historically reported the virus.
The US reports the third highest number of monkeypox infections, behind Spain and the United Kingdom, with 2107 confirmed cases.
When monkeypox viral infections first began in nonendemic countries in May 2022, health experts assured the public that smallpox vaccines could be deployed to effectively serve as pre-exposure prophylaxis for those with occupational hazards (i.e., healthcare providers) and as post-exposure prophylaxis for suspected cases and their close contacts. However, when New York City began booking monkeypox vaccine appointments on July 12, it became apparent that there were not enough doses to go around.
Thus, investigators are looking for other ways to combat the virus. There are no specific treatments licensed for monkeypox, but one study, published in JAMA, analyzed several preexisting drugs to determine whether any can be effectively deployed against the current outbreaks.
In a 2021 study, the antiviral brincidofovir was proven effective against orthopoxviruses in animal models. The orthopoxvirus family encompasses smallpox and monkeypox, but not chickenpox (varicella), which is a member of the herpes family. Brincidofovir was approved by the US Food and Drug Administration (FDA) to treat smallpox in June 2021. When given to healthy humans in phase 1 clinical trials, brincidofovir had a tolerable safety profile.
A local UK clinical trial was studying the drug for an unrelated illness, so the investigators were able to study brincidofovir’s efficacy in monkeypox patients. However, brincidofovir did not demonstrably improve the patients’ monkeypox symptoms. The treatment was halted when the patients developed elevated liver enzymes with no clinical benefit. The monkeypox infections were eventually resolved with other care.
Next, the investigators identified the oral smallpox therapy tecovirimat as another potential monkeypox antiviral. The drug had promising results in smallpox animal trials, as well as in a 2018 human study. The healthy adult volunteers had no concerning adverse events after receiving tecovirimat in a randomized safety trial.
Tecovirimat was put to the test against monkeypox in a 2021 study. This antiviral works by interfering with an orthopoxvirus envelope protein, which prevents virions from leaving infected cells. A patient treated with tecovirimat saw a complete stop in new monkeypox lesions after 24 hours, and within 48 hours, the patient’s blood and respiratory samples were negative for the virus.
“It was quite compelling when we compare the different patients and their clinical courses how quickly the 1 patient got better with tecovirimat,” said Hugh Adler, PhD, the lead author of the former study. He remains hopeful about brincidofovir for monkeypox, however, saying, “I don’t think our experience is enough to completely turn one’s back on brincidofovir.”
The investigators point out the obvious criticisms of the current race to find a monkeypox cure: all of this concern only arose once the virus came to Western countries. For decades, there have been thousands of monkeypox infections and hundreds of deaths in west and central African countries.
The US and other wealthy nations have been stockpiling the Jynneos and ACAM200 smallpox vaccines, without rolling them out to endemic countries. “The hope is that this current outbreak draws attention to how neglected monkeypox has been in western and central Africa,” Adler said. “If we just did the first research when it was there, we’d be in a better position.”