主页 > 医学信息 >
【drug-news】两亲性DNA聚合物可能成为一种新的抗
Senior author Dr. Andrew Vaillant, of REPLICor, Inc., in Laval, Quebec, Canada told Reuters Health that researchers have long been trying to develop the antiviral potential of polymers. His team has been using phosphorothioated oligonucleotides, which have sequence-independent antiviral activity as amphipathic polymers. "The mechanism of action of our DNA polymers is not susceptible to mutations," he said. "They act against the alpha helices on the surface of the virus, a very large target that's commonly conserved in most viruses."
"These compounds actually work against all enveloped viruses," giving them the potential to satisfy tremendous unmet medical needs, Dr. Vaillant said. He added that in addition to herpes simplex virus (HSV)-1/2 and cytomegalovirus (CMV), these compounds work against hepatitis C virus (HCV), hepatitis B virus (HBV), influenza, respiratory syncytial virus (RSV), even Ebola and Marburg viruses. REPLICor is also exploring their topical microbicidal activity against human immunodeficiency virus, he said.
"Our compounds are polymers but we use DNA," Dr. Vaillant said. "This chemistry allows us to achieve a much better chemical fit to the target on the virus and, as a naturally occurring chemistry in the body, these compounds are much less toxic than other polymers."
The research team had initially shown their amphipathic polymers to be effective against HSV when tested in vitro. Now, they report, "amphipathic polymers possess an even broader spectrum of activity than previously reported including potent in vitro activity against not only HSV-1 and HSV-2 and human CMV but also varicella-zoster virus, Epstein-Barr virus, and human herpesviruses 6A and 6B."
In the current paper, they evaluated the activity of REPLICor's compounds in a murine topical microbicide model of genital herpes simplex virus-2 (HSV-2) infection, "where the drug is applied prior to the virus challenge, because of the urgent need to develop more microbicide candidates that are safe and effective against a range of sexually transmitted pathogens."
One of these compounds, REP 9, in a dose of 275 mg/mL, "protected 75% of animals from disease and infection when provided 5 or 30 minutes prior to vaginal challenge," the investigators report.
The researchers then evaluated an acid stable form of the compound (REP 9C), because "it is important to maintain the acidic environment of the vagina as a natural protective mechanism." Using the acid stable analogue, "75% of mice were protected when treated with 240 mg/mL prior to infection (p < 0.001), while a lower dose (100 mg/mL) protected 100% of the mice (p < 0.001). The acid stable...formulation also provided protection at 30 min (83%, p < 0.001) and 60 minutes (50%, p = 0.07) against disease."
These compounds retain their activity in the presence of seminal fluid, the researchers note.
Dr. Vaillant points out that this was an early study, which confirms the compound's potential against HSV-2. "We expect the performance of the compound to improve significantly with the proper drug formulation," he said.
"We currently have papers in review describing the effectiveness of our compounds against CMV and HCV in vivo," he said. "Our priorities are to bring these compounds to market for treating hepatitis C recurrence after transplant and to treat existing HCV and HBV infections."
Antimicrob Agents Chemother 2008;52:2727-2733.
阅读本文的人还阅读：
作者:admin@医学,生命科学 2010-11-09 05:11
医学,生命科学网