Although smallpox was eradicated over 30 years ago, the disease remains a major threat. High mortality, high infectivity
and low resistance of the contemporary population make the smallpox virus very attractive to terrorists. The possible
presence of illegal stocks of the virus or risk of deliberate genetic modifications cause serious concerns among experts.
Hence, it is reasonable to seek effective drugs that could be used in case of smallpox outbreak. This paper reviews studies on
compounds with proven in vitro or in vivo antipoxviruses potential, which show various mechanisms of action. Nucleoside
analogues, such as cidofovir, can inhibit virus replication. Cidofovir derivatives are developed to improve the bioavailability
of the drug. Among the nucleoside analogues under current investigation are: ANO (adenozine N1-oxide) and its derivatives,
N-methanocarbothymidine [(N)-MCT], or derivatitives of aciklovir, peninclovir and brivudin. Recently, ST-246 – which
effectively inhibits infection by limiting release of progeny virions – has become an object of attention. It has been also
been demonstrated that compounds such as: nigericin, aptamers and peptides may have antiviral potential. An interesting
strategy to fight infections was presented in experiments aimed at defining the role of individual genes (E3L, K3L or C6L)
in the pathogenesis, and looking for their potential blockers. Additionally, among substances considered to be effective
in the treatment of smallpox cases, there are factors that can block viral inhibitors of the human complement system,
epidermal growth factor inhibitors or immunomodulators. Further studies on compounds with activity against poxviruses
are necessary in order to broaden the pool of available means that could be used in the case of a new outbreak of smallpox.
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