An Overview of Antivirals against Monkeypox Virus and Other Orthopoxviruses

The current monkeypox outbreaks during the COVID-19 pandemic have reignited interest in orthopoxvirus antivirals. Monkeypox belongs to the Orthopoxvirus genus of the Poxviridae family, which also includes the variola virus, vaccinia virus, and cowpox virus. Two orally bioavailable drugs, tecovirimat and brincidofovir, have been approved for treating smallpox infections. Given their human safety profiles and in vivo antiviral efficacy in animal models, both drugs have also been recommended to treat monkeypox infection. To facilitate the development of additional orthopoxvirus antivirals, we summarize the antiviral activity, mechanism of action, and mechanism of resistance of orthopoxvirus antivirals. This perspective covers both direct-acting and host-targeting antivirals with an emphasis on drug candidates showing in vivo antiviral efficacy in animal models. We hope to speed the orthopoxvirus antiviral drug discovery by providing medicinal chemists with insights into prioritizing proper drug targets and hits for further development.

 

Comments：

Tecovirimat (also known as ST-246) and brincidofovir (CMX001) are both approved by the US FDA for the treatment of smallpox infections, and both have shown in vivo efficacy against monkeypox in animal models. Tecovirimat works by inhibiting the formation of the virus's envelope, while brincidofovir is a prodrug that gets converted into cidofovir, a nucleotide analogue that inhibits DNA polymerase.

Aside from these two drugs, several other compounds have shown potential for the treatment of orthopoxvirus infections. One example is JNJ-63623872, which works by inhibiting the activity of the viral protein F13L, required for the formation of the virion. Another promising compound is CMLDBU10, which inhibits the activity of the virus's RNA polymerase.

Developing effective antivirals against orthopoxviruses is important, given the potential for outbreaks of smallpox or other related viruses. Furthermore, the emergence of monkeypox cases during the COVID-19 pandemic highlights the need for effective treatments for related viruses. Identifying new drug targets and developing novel antivirals may help in the fight against these deadly pathogens.

Related Products

Cat.No.	Product Name	Information
S3380	Tecovirimat	Tecovirimat is an antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. Tecovirimat is developed for the treatment of smallpox infection.

Related Targets

Antiviral