Antiviral medications that fight the monkeypox virus

Antiviral medications that fight the monkeypox virus

EDITED BY, SNEHA MAVIS

University of Oklahoma researchers have described three medications with antiviral activity against the monkeypox virus in a study published as an accepted paper in the journal Clinical Infectious Diseases (MPXV). 

Human monkeypox (hMPX) is a zoonosis transmitted by MPXV, a double-stranded (ds) DNA virus in the Orthopoxvirus genus. The first incidence of hMPX was reported in the Democratic Republic of the Congo in 1970. In addition to sporadic outbreaks in North America and Europe, West and Central Africa have had numerous outbreaks.

Two clades of MPXV—the Congo Basin (CB) and West African (WA) clades—have been identified through genomic research. Supportive care has been the main treatment for MPXV infections. The three antiviral medications brincidofovir (BCV), tecovirimat (ST-246), and cidofovir (CDV), which work against MPXV, were discussed in the current review.

Cidofovir:

CDV is a prodrug that is phosphorylated by host enzymes as soon as it enters a cell to become active CDV-diphosphate (CDV-pp). During replication, the active substance combines into the developing (viral) DNA strand and inhibits DNA synthesis. Infections with poxviruses have been treated in people with CDV. According to case studies, a multifaceted strategy for treating ocular cowpox included the intravenous administration of CDV. In a patient with vaccinated eczema, its combination usage with ST-246 has been recorded. In both children and adults, topical CDV has been used to treat molluscum contagiosum. Usually, after applying CDV, lesions have acute inflammation before radically healing.

Brincidofovir:

In 2021, BCV, a lipid-conjugated version of CDV, was authorized for the treatment of smallpox. Like CDV, BCV has a wide range of activity against dsDNA viruses. In contrast to CDV, BCV easily enters host cells due to its lipophilic nature. Phospholipases hydrolyze BCV into CDV, which is then phosphorylated to generate the active form (CDV-pp). The infection course of MPXV in prairie dogs is similar to that of people. BCV enhanced survival in these pups when delivered soon after MPXV exposure, demonstrating that early treatment is critical for efficacy.

Tecovirimat:

ST-246 was licensed in 2018 for the treatment of smallpox. The medication only affects orthopoxviruses and does not affect other dsDNA viruses. ST-246 specifically targets the gene encoding p37, a conserved membrane protein responsible for the formation of the virus's extracellular envelope. Protein/DNA synthesis and viral maturation are not hampered by ST-246. It has been successful in treating MPXV in macaques and prairie dogs. In many animal models, giving ST-246 within 72 hours of poxvirus exposure was effective in lowering lesion severity and decreasing mortality.

Synergistic action is produced when ST-246 and BCV are administered together. For instance, combination therapy reduced mortality relative to individual drug treatment in mice with cowpox infection.