The chloroxoquinolinic derivative 6-chloro-1,4-dihydro-4-oxo-1-(beta-D-ribofuranosyl) quinoline-3-carboxylic acid inhibits HSV-1 adsorption by impairing its adsorption on HVEM.

In this paper, we describe that the oxoquinolinic acid derivative (compound A) inhibited HSV-1 adsorption on Vero cells. This effect was achieved with an EC(50) value of 10 +/- 2.0 microM and with low cytotoxicity, since the CC(50) value for compound A was >1000 microM. Moreover, we demonstrate for the first time that adsorption inhibition was due to the blockage of the interactions between HSV-1 and the cellular receptor herpes virus entry mediator (HVEM). These results show that compound A can prevent HSV-1 infection in Vero cells, encouraging further studies to determine at what level compound A inhibits HSV-1-HVEM interactions.

Antiviral activity of diterpenes isolated from the Brazilian marine alga Dictyota menstrualis against human immunodeficiency virus type 1 (HIV-1).

The antiviral effect of the CH(2)Cl(2)/MeOH-soluble fraction from the alga Dictyota menstrualis on HIV-1 replication was evaluated in vitro. The antiretroviral activity was attributed to two diterpenes: (6R)-6-hydroxydichotoma-3,14-diene-1,17-dial, named Da-1, and (6R)-6-acetoxi-dichotoma-3,14-diene-1,17-dial, named AcDa-1. Da-1 or AcDa-1 were added to the culture medium of HIV-1-infected PM-1 cells at different times post-infection or during virus adsorption/penetration. The results indicated that the compounds affected an early step of the virus replicative cycle. Virus binding and entry into the host cells were evaluated in the presence of each diterpene, but no inhibitory effect was observed. To evaluate provirus DNA synthesis/integration into the host genome, the viral protease coding sequence was amplified from total cellular DNA. Proviral DNA was not detected in infected cells incubated with the diterpenes. To investigate the effect of the diterpenes on the reverse transcription of the viral genomic RNA, the recombinant HIV-1 reverse transcriptase (RT) was assayed in vitro in the presence of each diterpene. Da-1 and AcDa-1 inhibited the RNA-dependent DNA-polymerase activity of HIV-1 RT in a dose-dependent manner. Taken together, our results demonstrate that both diterpenes inhibit HIV-1 RT and consequently virus replication.

Inibiçäo seletiva das atividades das enzimas transcriptase reversa do vírus HIV-1 e DNA polimerases humanas por derivados dipirazolo-piridina / Selective inhibition of reverse transcriptase enzyme activity of HIV-1 virus and human polymerases DNA by dipirazolo-pyridines derivatives

Novos ribonucleosídeos derivados dos sistemas dipirazolo-piridina foram preparados e avaliados quanto à atividade polimerásica das enzimas transcriptase reversa (RT) do vírus HIV-1 e das DNA polimerases humanas alfa e epsilon. Os derivados 1b e 1d inibiram a atividade da transcriptase reversa em concentraçöes de micromolares. Entretanto, as mesmas substâncias näo foram capazes de inibir a atividade polimerase das enzimas DNA-polimerase humana alfa e epsilon.

Human papillomavirus detection in genital lesions by in situ hybridization and ultrastructural observations

Detection of papillomavirus DNA in sity hybridization technique was perfomed in 29 symptomatic patients (6 males and 23 females) during the period of 1989-1991 at the Clinic for Sexually Transmitted Diseases, Universidade Federal Fluminense, State of rio de Janeiro. All the male patients had condyloma acuminata. Only HPV 6/11 were found in these lesions. Clinical features inthe female patients included vulvar condyloma acuminata, bowenoid populosis, flat cervical condyloma, cervical condyloma acuminatum and cervical intraepithelialneoplasia grade II (CIN II). We also found cases of condyloma acuminata associated to vulvar intraepithelial neoplasia grade III (VIN III), as well as to vaginal invasive carcinoma. HPV 6/11 and 16/18 were found in vulvar condyloma acuminata. Mixed infection by 6/11-16/18 HPV were also seen in these lesions as well as in the patient who had cervical condyloma acuminatum. HPV 16/18 were found in the condyloma acuminatum plus VIN III and in the CIN II lesions. We have found HPV31/33/51 in the specimen of condyloma acuminatum plus invasive carcinoma. In order to investigate the ultrastructural aspects of HPV infection in genital tissue, the biopsies of three female patients were observed under electron microscope.Mature virus particles were found in the cells of a condyloma acuminatum as wellas in the condyloma acuminatum plus invasive carcinoma case. In another sample, chromosome breakages were found in the nuclei of the infected cells although no viral particles were observed