Research on substances with activity against orthopoxviruses

Area of Science:

• Virology
• Pharmacology
• Infectious Diseases

Background:

• Smallpox, though eradicated, poses a significant bioterrorism threat due to high infectivity and low population immunity.
• Concerns exist regarding illicit virus stocks and potential genetic modifications, underscoring the need for effective countermeasures.
• The contemporary population's low resistance to smallpox necessitates the development of novel antiviral therapies.

Purpose of the Study:

• To review existing research on compounds with demonstrated in vitro or in vivo antiviral activity against poxviruses.
• To identify diverse mechanisms of action employed by potential smallpox therapeutics.
• To highlight promising drug candidates and therapeutic strategies for managing smallpox outbreaks.

Main Methods:

• Literature review of studies investigating antipoxviral compounds.
• Analysis of compounds targeting viral replication, virion release, and host-pathogen interactions.
• Examination of research on nucleoside analogues, ST-246, nigericin, aptamers, peptides, gene-targeting agents, and immunomodulators.

Main Results:

• Nucleoside analogues (e.g., cidofovir, its derivatives, ANO, (N)-MCT, acyclovir, penciclovir, brivudine) inhibit viral replication.
• ST-246 effectively limits the release of progeny virions, showing significant antiviral potential.
• Other compounds like nigericin, aptamers, peptides, gene blockers, complement inhibitors, and immunomodulators also exhibit antipoxviral activity.

Conclusions:

• A variety of compounds, including nucleoside analogues and ST-246, demonstrate significant potential for treating smallpox.
• Targeting viral genes (E3L, K3L, C6L) and host-pathogen interactions offers novel therapeutic avenues.
• Continued research is crucial to expand the arsenal of effective treatments against potential smallpox outbreaks.