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7. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

Author

Juteau Jean-Marc, Flamand Louis, Cummins James, Sewell Andrea P, Bravo Fernando J, Cardin Rhonda D, Bernstein David I, and Vaillant Andrew

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Phosphorothioated oligonucleotides (PS-ONs) have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs) and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV) infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9) inhibited both murine CMV (MCMV) and guinea pig CMV (GPCMV) with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C) inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs) was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated antiviral activity against CMV infection in vivo and represent a new class of broad spectrum anti-herpetic agents.

Published
2009
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15. Sequencing of Comamonas testosteroni strain B-356-biphenyl/chlorobiphenyl dioxygenase genes: evolutionary relationships among Gram-negative bacterial biphenyl dioxygenases

Author

Sylvestre, Michel, primary, Sirois, Marc, additional, Hurtubise, Yves, additional, Bergeron, Janique, additional, Ahmad, Darakhshan, additional, Shareck, François, additional, Barriault, Diane, additional, Guillemette, Isabelle, additional, and Juteau, Jean Marc, additional

Published
1996
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16. Sequence of the bphD gene encoding 2-hydroxy-6-oxo-(phenyl/ chlorophenyl)hexa-2,4-dienoic acid (HOP/cPDA) hydrolase involved in the biphenyl/polychlorinated biphenyl degradation pathway in Comamonas testosteroni: Evidence suggesting involvement of Ser112 in catalytic activity

Author

Ahmad, Darakhshan, primary, Fraser, Judith, additional, Sylvestre, Michel, additional, Larose, Angéle, additional, Khan, Atif, additional, Bergeron, Janique, additional, Juteau, Jean Marc, additional, and Sondossi, Mohammad, additional

Published
1995
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