Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf

Abstract

Therapeutic and vaccine development for human poxvirus infections (e.g., monkeypox (mpox) virus, variola virus, molluscum contagiosum virus, orf virus) has been largely deserted, especially after the eradication of smallpox by 1980. Human mpox is a self-limited disease confined to Central and West Africa for decades. However, since April 2022, mpox has quickly emerged as a multi-country outbreak, urgently calling for effective antiviral agents and vaccines to control mpox. Here, this review highlights possible therapeutic options (e.g., tecovirimat, brincidofovir, cidofovir) and other strategies (e.g., vaccines, intravenous vaccinia immune globulin) for the management of human poxvirus infections worldwide.

Keywords: Brincidofovir; Cidofovir; Monkeypox(mpox); Smallpox; Tecovirimat.

Fig. 1

The Poxviridae family tree. Human poxviruses from the Chordopoxvirinae subfamily have been highlighted. Recurrent, rare, and eradicated infections are indicated by red, blue, and green designations, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

A geographical map of mpox cases (A) The total number of mpox cases (years: 1970 to 2017) in West and Central Africa was collected from the WHO survey [17]. (B) The geographical distribution of total mpox cases from 2022/01/01 to 2022/11/30. The data was collected from the US CDC (https://www.cdc.gov/poxvirus/monkeypox).

Fig. 3

Electron micrograph images (A) and clinical images (B) of mpox, smallpox, molluscum contagiosum, and orf in humans. The micrograph and clinical images for mpox [by Charles D. Humphrey, Tiara Morehead, Russell Regnery, Brian W.J. Mahy], smallpox [by Cynthia S. Goldsmith, Russell Regnery], vaccinia virus [by Moses Grossman], orf virus [by Maureen Metcalfe, Tom Hodge, James H. Nakano], and molluscum contagiosum [by James H. Nakano, Susan Lindsley] were obtained from the Centers for Disease Control and Prevention [http://phil.cdc.gov/phil/home.asp] with the permission for free publication.

Fig. 4

Antiviral agents for human poxvirus infections. (A) Kaplan–Meier plot of vaccine versus cidofovir and HPMPO-DAPy with the post-exposure effect on the survival of macaques (this subfigure was copied from our previous publication [35]). Arrowheads show the time points of vaccination or antiviral treatment. After intratracheal mpox infection, macaques were sham-treated (group I), vaccinated with smallpox vaccine Elstree-RIVM (group II), treated with five-dose cidofovir (group III), with six-dose cidofovir (group IV), with five-dose HPMPO-DAPy (group V) or with six-dose HPMPO-DAPy (group VI) [35]. Chemical structures of cidofovir (B), HPMPO-DAPy (C), tecovirimat (D), and brincidofovir (E).