Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.
ABSTRACT Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.
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ABSTRACT: Camelpox is considered as emerging public health problem during this decade due to increased reported cases and outbreaks in camels. Camelpox is a contagious, often sporadic, and notifiable skin disease of camelids and is socio-economically significant as it incurs considerable loss in terms of morbidity, mortality, loss of weight and reduction in milk yield and confined to camel-rearing countries. The causative agent, camelpox virus (CMLV) is genetically closely related to variola virus and has gained much attention from researchers due to its recent emergence in human. The virus carrying genes responsible for host immune evasion mechanisms owing to the threat posed by potential bio-warfare agents. Although the disease can be diagnosed based on clinical features, the similar confounding skin lesions necessitate identification, detection and differentiation of the CMLV by molecular techniques. Vaccines are available in some countries and the available live attenuated vaccine provides long-lasting immunity. Further, novel highly sensitive and specific techniques would be useful in the identification of emerging and re-emerging virus, thereby therapeutic, prophylactic, preventive measures would be applied in time to curtail further spread of camelpox like other zoonotic diseases. This review provide overview of the camelpox particularly on its epidemiology, pathogenesis and biology of the disease, diagnostic approaches and control measures.Indian Journal of Virology 12/2013; 24(3). DOI:10.1007/s13337-013-0145-0 · 0.36 Impact Factor
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ABSTRACT: Prominent in the current stage of antiviral drug development are: (i) for human immunodeficiency virus (HIV), the use of fixed-dose combinations (FDCs), the most recent example being Stribild(TM) ; (ii) for hepatitis C virus (HCV), the pleiade of direct-acting antivirals (DAAs) that should be formulated in the most appropriate combinations so as to obtain a cure of the infection; (iii)-(v) new strategies (i.e., AIC316, AIC246, and FV-100) for the treatment of herpesvirus infections: herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), respectively; (vi) the role of a new tenofovir prodrug, tenofovir alafenamide (TAF) (GS-7340) for the treatment of HIV infections; (vii) the potential use of poxvirus inhibitors (CMX001 and ST-246); (viii) the usefulness of new influenza virus inhibitors (peramivir and laninamivir octanoate); (ix) the position of the hepatitis B virus (HBV) inhibitors [lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate (TDF)]; and (x) the potential of new compounds such as FGI-103, FGI-104, FGI-106, dUY11, and LJ-001 for the treatment of filoviruses (i.e., Ebola). Whereas for HIV and HCV therapy is aimed at multiple-drug combinations, for all other viruses, HSV, CMV, VZV, pox, influenza, HBV, and filoviruses, current strategies are based on the use of single compounds.Medicinal Research Reviews 03/2013; 33(6). DOI:10.1002/med.21281 · 8.13 Impact Factor
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ABSTRACT: The last years, cowpox infections are being increasingly reported through Eurasia. Cowpox viruses (CPXVs) have been reported to have different genotypes and may be subdivided in at least five genetically distinct monophyletic clusters. However, little is known about their and features. In this report, five genetically diverse CPXVs, including one reference strain (CPXV strain Brighton) and four clinical isolates from human and animal cases, were compared with regard to growth in cells, pathogenicity in mice and inhibition by antivirals. While all CPXVs replicated similarly and showed comparable antiviral susceptibility, marked discrepancies were seen , including differences in virulence with recorded mortality rates of 0%, 20% and 100%. The four CPXV clinical isolates appeared less pathogenic than two reference strains, CPXV Brighton and vaccinia virus Western-Reserve. Disease severity seemed to correlate with high viral DNA loads in several organs, virus titers in lung tissues and levels of IL-6 cytokine in the sera. Our study highlighted that the species CPXV consists of viruses that not only differ considerably in their genotypes but also in their phenotypes, indicating that CPXVs should not be longer classified as a single species. Lung virus titers and IL-6 cytokine level in mice may be used as biomarkers for predicting disease severity. We further demonstrated the potential benefit of cidofovir, CMX001 and ST-246 use as antiviral therapy.PLoS ONE 02/2013; 8(2):e55808. DOI:10.1371/journal.pone.0055808 · 3.53 Impact Factor