Thieno[2,3-b]pyridine derivatives: a new class of antiviral drugs against Mayaro virus.

Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.

Antiproliferative effect of indomethacin in Aedes albopictus (mosquito) cells

Non-steroidal and anti-inflammatory drugs (NSAIDs) are a class of pharmacological agents that are tradicionally used for their anti-cyclooxigenase properties in the treatment of inflammation and other associated diseases. Recently, however, it has been demonstrated that several NSAIDs exhibit antiproliferative effects in various animal models and in vitro experiments. In this paper we demonstrated that treatment of Aedes albopictus cells (mosquito) with indomethacin results in a reduction of normal growth rate. Cells treated with 100 mM indomethacin exhibited a profound time dependent reduction in their proliferation rate over the 96 h test period.

Classical Swine Fever in Brazil: study for the survey of classical swine fever outbreaks in Brazil from 1978 to 2004 / Peste Suína Clássica no Brasil: estudo para a avaliação dos surtos depeste suína clássica no Brasil de 1978 a 2004

The programs developed in Brazil with the aim to control and eradicate swine fever provided an opportunityfor the survey of Classical Swine Fever (CSF) outbreaks. Were concerned CSF official programs, strategies and results, during 26 years. Based in epizootic official data we showed that the number of CSF outbreaks from 1978 to 2004 drastically decreased in all country, although different eradicating strategies were applied in those official programs, especially in fourteen States of "CSF Free Zone". Were evaluated both CSF official programs: Swine Pests Combat Program (SPCP) from 1984 to 1991 and CSF Eradication and Control Program (CSFECP) from 1992 to 2004 by the decreasing of CSF outbreaks number. Considering the technical evolution in swine production systems, statistical analysis to compare the ranking of CSFoutbreaks in each program was performed by Mann-Whitney test, that showed at 95% confidence level(Table T) a significant difference (p< 0.05) between programs, as suggested in CSF outbreaks profileplotted diagram. The number of CSF outbreaks occurred from 2000­2004 in "CSF-infected" and "CSF-free" zones, was analyzed. Also, we regarded with most important recent CSF outbreak in Brazil occurred in 1997, during CSFECP, that was figured out by stamping out measures without appealing to preventive vaccination regimen. Those results suggest that the efficacy of implemented CSF eradication programs depends on the continuity of defined strategies as rigorous vigilance, notification, virus diagnostic screening and sanitary police measures in order to enable quick and adequate action upon CSFV detection

Os programas oficiais para o controle e erradicação de pestes suínas forneceram uma oportunidade de levantar o perfil de ocorrência da Peste Suína Clássica (PSC). Independente das estratégias aplicadasdurante 26 anos foi demonstrado que o número de surtos de PSC de 1978 até 2004 caiu drasticamente emtodo país, especialmente nos quatorze Estados inclusos na "Zona Livre de PSC". O estudo comparou o número de surtos de PSC durante a vigência do Programa de Combate às Pestes Suínas (PCPS) de 1984a 1991 e o Programa de Controle e Erradicação da PSC (PCEPSC) de 1992 a 2004. Considerando aevolução tecnológica nos sistemas de produção de suínos, a diferença nos resultados obtidos após aimplementação de cada programa foi avaliada pelo teste estatístico Mann Whitney por meio da ordenaçãodo número de surtos ocorridos. Essa análise demonstrou uma diferença significativa (p< 0,05) entre osprogramas no nível de confiança de 95% (Tabela T) com havia sido sugerido pelo diagrama do perfil deocorrência da PSC. A eficácia do PCEPSC para debelar o mais importante surto de PSC ocorridorecentemente no Brasil, em 1997, também foi considerada. Paralelamente, o número de surtos ocorridosde 2000 a 2004 nas áreas infectadas com a PSC e na zona livre de PSC foi avaliado. Os resultados sugeremque a eficácia dos programas de erradicação depende da continuidade das estratégias definidas como avigilância rigorosa, notificação, rastreamento do vírus e medidas sanitárias que agilizem a ação nomomento de detecção de vírus da PSC

In vitro antiviral diterpenes from the Brazilian brown alga Dictyota pfaffii.

Specimens of Dictyota pfaffii from Atol das Rocas, Northeast Brazil, afforded the rare dolabellane diterpene 10,18-diacetoxy-8-hydroxy-2, 6-dolabelladiene (1) and the new 10-acetoxy-8,18-di-hydroxy-2,6-dolabelladiene (2). Reduction of 1 yielded 8,10,18-trihydroxy-2,6-dolabelladiene (3), also present in the crude ex-tract of D. pfaffii. All three structures were assigned by 1D and 2D NMR spectral data. These substances showed strong anti-HSV-1 activity in vitro but only 3 inhibited the reverse transcriptase enzyme of HIV-1.

Effect of prostaglandin A1 in porcine cells persistently infected with classical swine fever virus.

Cyclopentenone prostaglandins are potent inhibitors of a wide variety of RNA and DNA viruses. In this report we describe that prostaglandin A1 (PGA1) potently inhibited the replication of classical swine fever virus in cultures of PK-15 cells. The highest non-toxic dose (5 microg/ml) inhibited virus yield in 99% at the initial phase of infection and in 77% in persistent infected cells. However when PGA1 was removed from persistently infected cells, the inhibition of virus replication was partially reverted.

Prostaglandin A1, inhibits replication of Classical Swine Fever Virus

Prostaglandins (Pgs) have been shown to inhibit the replication of several DNA and RNA viruses. Here we report the effect of prostaglandin (PgA1) on the multiplication of a positive strand RNA virus, Classical Swine Fever Virus (CSFV) in PK15 cells. PgA1 was found to inhibit the multiplication of CSFV. At a concentration of 5 µg/ml, which was nontoxic to the cell, PgA1 inhibits virus production in 99 per cent. In PgA1 treated cells the size and number of characteristic Classical Swine Fever focus decreased in amount.