Monkeypox (MPX) - Family Poxviridae, genus Ortopoxvirus
Since may 2022 and as of October 2022 >70 000 cases reported from 100 countries - most
of which with no historical stated MPX infections (>24 000 cases in Europe), and 26
confirmed deaths; WHO declared the MPX outbreak a global health emergency on 23 July
2022.
Phylogenetically, two main genetic clades were described to date, the Central African
(Congo Basin) clade and the West African clade, the first considered to be more
transmissible and more virulent; the only country where both clades have been found
coexisting is Cameroon.
https://www.who.int/news-room/fact-sheets/detail/monkeypox
The recent outbreak is produced by lineage B.1 of the West African clade, also designated
as MPXV Clade 3, with 46 characteristic individual SNPs (24 non-synonymous SNPs), and
displaying a high rate of genomic variability.
Viral life cycle of MPX
Poxviral particles (enveloped, dsDNA) bind to receptors from the host cells; the fusion with
the cell membrane leads to the injection of the cores (containing dsDNA genome, enzymes,
and transcription factors) into the cytoplasm of the host cell. The replication of Poxviruses
takes place into the cytoplasm of the host cell. The genome is transcribed in three types of
messenger RNAs (mRNAs – early, intermediate, and late) that are translated into numerous
proteins.
Maturation implies the creation of infectious intracellular mature virions (MV), which are
wrapped by modified trans-Golgi and endosomal cisternae, producing the wrapped virions
(WV); the latter are transported to the periphery of the cell via microtubules, and fuse with the
plasma membrane (actine tails), releasing the extracellular enveloped virions (EV).
Symptoms of MPX infection: fever, headache, muscle aches, back pain, anergy and swollen
lymph nodes, followed or accompanied by the development of a characteristic vesicular
rash which may last for two to three weeks.
Approved Treatment for MPX
1. Tecovirimat (TPOXX, ST-246)
Tecovirimat SIGA is the only antiviral authorized in the European Union to treat smallpox,
monkeypox and cowpox.
Molecular target is VP37, a 37,000-Da protein found on the surface of OPX, encoded by the
viral F13L gene, necessary for the membrane envelopment of intracellular mature virus
(MV), followed by the formation of the wrapped virus (WV).
2. Cidofovir (CDV, Vistide) and Brincidofovir (BCV, CMX001 or Tembexa)
Cidofovir is an DNA polymerase inhibitor approved for the treatment of cytomegalovirus
(CMV) retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS).
Brincidofovir demonstrated antiviral activity against double-stranded DNA viruses, including
poxviruses. Brincidofovir is a DNA polymerase inhibitor, approved in 2021 for the treatment
of human smallpox infection in adults and children
3. Vaccinia Immune Globulin (VIG) is licensed by FDA for the treatment of complications
due to vaccinia vaccination including eczema vaccinatum, progressive vaccinia, severe
generalized vaccinia,
Prevention
Two generations of vaccines are approved for pre-exposure prophylaxis of smallpox, as well
as for other ortopoxviruses/monkeypox:
- ACAM2000 - the live vaccinia vaccine of second-generation,
- JYNNEOS - the modified vaccinia Ankara strain (MVA), a third-generation vaccine.
References
1. Kimball, S. WHO declares rapidly spreading monkeypox outbreak a global health
emergency. CNBC https://www.cnbc.com/2022/07/23/whodeclares- spreadingmonkeypox-outbreak- a-globalhealth- emergency.html (2022).
2. ECDC European Centers for Disease Control. Epidemiological update: Monkeypox
multi-country outbreak. https://www.ecdc.europa.eu/en/news-events/epidemiologicalupdate-monkeypox-multi-country-outbreak-15-june
3. Isidro, J. et al. Phylogenomic characterization and signs of microevolution in the 2022
multi- country outbreak of monkeypox virus. Nat. Med. https://
doi.org/10.1038/s41591-022-01907-y (2022).
4. Luna, N. et al. Phylogenomic analysis of the monkeypox virus (MPXV) 2022
outbreak: emergence of a novel viral lineage. Travel. Med. Infect. Dis. https://
doi.org/10.1016/j.tmaid.2022.102402 (2022).
5. WHO. https://www.who.int/news-room/fact-sheets/detail/monkeypox
6. Smith GL, Vanderplasschen A, Law M. The formation and function of extracellular
enveloped vaccinia virus. J Gen Virol. 2002;83(Pt 12):2915–2931.
7. EMA. https://www.ema.europa.eu/en/medicines/human/EPAR/tecovirimat-siga
8. Thornhill, J. P. et al. Monkeypox virus infection in humans across 16 countries —
April–June 2022. N. Engl. J. Med. https://doi.org/10.1056/ NEJMoa2207323 (2022)