Three Previously Approved Treatments Show Anti-monkeypox Activity

A study published on August 2 details three drugs that have the potential to treat monkeypox. Atovaquone, mefloquine, and molnupiravir displayed far more potent anti-monkeypox activity than current anti-viral drugs. 

Related Article: BD, CerTest Commercialize Research-Use Monkeypox Test Amidst Rising Cases

Is the Treatment for Monkeypox Already Approved?

The anti-viral medications tecovirimat and brincidofovir are treatments for smallpox approved by the US Food and Drug Administration (FDA). Tecovirimat targets a significant protein of smallpox, known as VP37, and prevents it from leaving an infected cell. Brincidofovir, a modified version of another anti-viral drug known as cidofovir, enters an infected cell and prevents virus DNA from replicating.

However, a group of researchers in Japan have doubts about the effectiveness of these drugs’ treatment of monkeypox, another virus in the smallpox family. A study conducted at the Research Center for Drug and Vaccine Development, National Institute of Infectious in Tokyo, tested the efficacy of previously approved drugs’ treatment of monkeypox. 

The team focused on 132 clinically approved drugs using a cell-based monkeypox infection screening approach. These included anti-viral, anti-fungal, and anti-parasitic/anti-protozoal agents, as they include drugs containing a wide range of anti-viral activity.

The initial test for the 132 previously approved drugs was administering them to Vero E6 cells, cells extracted from African green monkeys, infected with monkeypox. Seventy-two hours after the initial infection, the researchers observed that 21 drugs showed positive results in treating the virus. However, the three that the researchers chose to focus on showed dramatic anti-monkeypox activity.

Inhibiting Monkeypox Before and After Cell Entry 

The three previously approved drugs were atovaquone, an antibiotic treating Pneumocystis jiroveci pneumonia (PCP), molnupiravir, the anti-viral factor in a COVID-19 treatment produced by Merck, and mefloquine, an anti-malarial treatment. 

Upon whittling the testing pool down to these three, the team focused on examining what specific part of monkeypox production each drug inhibited. 

Mefloquine appears to inhibit virus entry to a cell. This finding aligns with other reports claiming it does the same with COVID-19 and the Ebola virus. 

On the other hand, atovaquone and molnupiravir appear to inhibit the virus after it has already entered the cell. Specifically, atovaquone inhibits the replication of DHODH, an enzyme found in the mitochondria in monkeypox. By preventing this enzyme from replicating, it severely impairs monkeypox from replicating at all. These findings align with atovaquone’s other reported prevention of reproducing other poxviruses. Specifically, these include the Cantagolo virus, vaccinia virus, and cowpox virus.

Finally, molnupiravir demonstrated that it prevented the genome of monkeypox from polymerizing. This lines up with molnupiravir’s other reported polymerization presentations, specifically in hepatitis C virus, norovirus, chikungunya virus, and coronaviruses.

The study’s findings indicate that currently approved drugs could be critical treatments for monkeypox. However, other researchers have yet to peer review it. Should other teams come to similar conclusions, approved treatments for monkeypox may be available sooner than expected. 

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Author

Max Heirich