Antimurine retroviral effect of doxycycline.

The tetracycline family is composed of several molecules whose antibacterial properties are due to the fixation on the bacterial ribosomes. Among those, doxycycline is one of the most potent antibiotics for which additional features have been recently discovered. Doxycycline has been found to inhibit metalloproteinases, to decrease gelatinolytic and metastatic activities of cancer cells, to have a "chondroprotective" effect in inflammatory arthritides, and to have strong antimalarial properties. In this study, a murine retrovirus producing cell line (psi CRIP-pXT1) was incubated in variable concentrations of doxycycline. The retroviral titer of this cell line was measured by the ability to transfer resistance to G418 to NIH/3T3 cells. The retroviral titer was significantly decreased by 70% when the packaging cells had been incubated with 25 microM of doxycycline at 37 degrees C. The ID50 was around 8 micrograms/ml. Astonishingly, this effect was not observed at 32 degrees C. The mechanism of this effect is still to be determined. It may be useful to be aware of this effect for uncovering all of the possible antiviral qualities of doxycycline and its related molecules, such as glycylcyclines or anthracyclines.

[Antiviral activity of hydroalcoholic extract from Haemanthus albiflos on the Moloney murine leukemia virus and the human immunodeficiency virus]. / Activité antivirale d'un extrait hydro-alcoolique d'Haemanthus albiflos sur le virus de la leucémie murine de Moloney et le virus du syndrome de l'immunodéficience acquise.

We have used a biological test on the microplates of cellular cultures in order to investigate the toxicity and the antiviral properties against different viruses: defective Moloney Murine Leukemia virus (MoMLV) derived from the SVX shuttle and expressing resistance to the G418 antimitotic, and Human Immunodeficiency Virus (HIV) of a hydroalcoholic extract from Haemanthus albiflos (Amaryllidacae). The toxicity was assessed through coloric test evaluation of fixed cells stained with crystal violet. In a population of NIH 3T3 cells (Fibroblasts mouse), the toxicity found with 2, 7, 14 and 28 microliters/ml of lyophilisat extract corresponding at: 0.23, 0.81, 1.62 and 3.24 mg of plant dry, was 32, 50, 63 and 70% respectively. With regards to the antiviral properties, the plant extracts showed an inhibition of 88% on the formation of G418 resistant 3T3 clones. The assay on HIV infected lymphotic cells (P4) showed an IC50 of 4 microliters/ml for this extract plant. Therefore, the toxic effect was similar to the antiviral response.

Identification of a hexapeptide inhibitor of the human immunodeficiency virus integrase protein by using a combinatorial chemical library.

Integration of human immunodeficiency virus (HIV) DNA into the human genome requires the virus-encoded integrase (IN) protein, and therefore the IN protein is a suitable target for antiviral strategies. To find a potent HIV IN inhibitor, we screened a "synthetic peptide combinatorial library." We identified a hexapeptide with the sequence HCKFWW that inhibits IN-mediated 3'-processing and integration with an IC50 of 2 microM. The peptide is active on IN proteins from other retroviruses such as HIV-2, feline immunodeficiency virus, and Moloney murine leukemia virus, supporting the notion that a conserved region of IN is targeted. The hexapeptide was also tested in the disintegration reaction. This phosphoryl-transfer reaction can be carried out by the catalytic core of IN alone, and the peptide HCKFWW was found to inhibit this reaction, suggesting that the hexapeptide acts at or near the catalytic site of IN. Identification of an IN hexapeptide inhibitor provides proof of concept for the approach, and, moreover, this peptide may be useful for structure-function analysis of IN.

Inhibition of Moloney murine leukemia virus reverse transcriptase activity by tetrahydroxyxanthones isolated from the Chinese herb, Tripterospermum lanceolatum (Hyata).

Five tetrahydroxyxanthones (THXs) isolated from Tripterospermum lanceolatum (Hyata) have been shown to have a strong inhibitory effect on Moloney murine leukemia virus reverse transcriptase (Mo-MLV RT) activity when (rA)n-(dT)15 and (rC)n-(dT)12-18 were used as template-primers. 50% inhibitory concentrations of 1,3,5,6-THX, 2,3,6,7-THX 1,3,6,7-THX, 3,4,5,6-THX, and 3,4,6,7-THX were determined to be 0.15, 0.27, 0.58, 0.12, and 0.12 microM, respectively. Their effects were concentration-dependent, and the mode of inhibition was found to be by competitive inhibition with respect to template-primer. The tetrahydroxyl groups of THXs were shown to be important for their inhibitory activity. Acylation of THXs with various groups resulted in a moderate or strong decrease in their inhibitory activity.