Featured Research

from universities, journals, and other organizations

Novel Antiviral Drug Concept Targets Number Of Human Viruses

Date:
April 25, 2000
Source:
University Of Pennsylvania Medical Center
Summary:
In laboratory studies, an entirely new approach to antiviral drug development is showing remarkable effectiveness against herpes viruses, a large family of viruses associated with many human diseases. In addition, the innovative strategy targets these viruses at such a fundamental level that it may prove useful against a wide array of other viruses.

April 20, 2000 -- In laboratory studies, an entirely new approach to antiviral drug development is showing remarkable effectiveness against herpes viruses, a large family of viruses associated with many human diseases. In addition, the innovative strategy targets these viruses at such a fundamental level that it may prove useful against a wide array of other viruses. And because the approach attacks viruses indirectly by making the cells they infect profoundly inhospitable to them, the likelihood that viral drug resistance will develop is thought to be extremely low.

University of Pennsylvania Medical Center researchers reported the findings in a study presented today at the Thirteenth International Conference on Antiviral Research in Baltimore, MD.

"This is a novel approach to the development of antiviral drugs," says Luis M. Schang, Ph.D., a postdoctoral fellow and first author on the study. "In the laboratory, we and others are seeing significant viral inhibition with drugs that have no toxicity to cells. If the strategy shows similar success in animals and, eventually, in humans, it should be applicable against many different kinds of viral infections."

Schang emphasizes that a good deal of work remains to be done before the new approach can be validated as a viable treatment for viral infections in humans.

Until now, antiviral drugs have sought to attack viruses directly by interfering with essential proteins produced by the viruses. Scientists have long known, however, that viruses are parasites and depend on the cells they infect for crucial support of their life cycles. Using the herpes simplex virus (HSV) as model target, the Penn team discovered that by inhibiting a particular set of cellular enzymes upon which the virus depends they can successfully block all viral activity while causing the host cells no ill effects.

"To date, all effective anti-viral drugs target viral proteins because the thought has been that knocking out a cellular protein would kill the cell," says Priscilla A. Schaffer, Ph.D., chair of microbiology and senior author on the study. "We've discovered that's not true -- by inhibiting a specific type of cellular enzyme, we've been able to completely block all viral activity without damaging the cells."

The pivotal enzymes are called cyclin-dependent kinases, or cdks. Cells use cdks, along with other proteins, to drive and coordinate cell division. Many viruses, too, rely on cellular cdks for their replication.

The Penn scientists were aware that Laurent Meijer, Ph.D., and his colleagues at the Centre National de la Recherche Scientifique in Roscoff, France, had developed and characterized a variety of cdk-specific inhibitors. With Meijer's assistance, they introduced his inhibitors into HSV-infected cells to test their antiviral theory. What they found was that viral replication ceased while the cells continued to be healthy.

Since the cells depend on cdks for their division but not for many other essential functions, they simply stop dividing in the presence of the drugs. But HSV depends absolutely on cdks for at least three steps in its life cycle, as is likely the case for other viruses, making it vulnerable to cdk inhibitors in multiple ways.

Additionally, the focused reliance of the viruses on cdks, combined with the fact that cdks are cellular, not viral, proteins, strongly suggests that the viruses will have a vanishingly small chance of mutating to develop resistance to cdk inhibitors.

Among the strains of virus completely inactivated by the cdk inhibitors in the Penn experiments were HSV-1 and HSV-2, which chronically infect 80 percent and 20 percent of the world's population respectively and are responsible for painful oral, and genital lesions, themselves a risk factor for sexually transmitted diseases and other health problems. HSV infections can also result in blindness and occasionally in fatal encephalitis.

Thomas Albrecht, Ph.D., and his team at the University of Texas, Galveston, have shown that another herpes virus, human cytomegalovirus, or HCMV, is also inhibited by cdk inhibitors. HCMV chronically infects 80 percent of people worldwide and can be life threatening in immunocompromised individuals such as transplant recipients and cancer patients. Epstein-Barr virus, responsible for infectious mononucleosis, is a virus in the herpes family that the scientists also expect will respond to treatment with cdk inhibitors, although this has yet to be tested.

Indeed, most viruses that replicate in the cell nucleus are potential candidates for the cdk inhibitor antiviral approach, according to the Penn scientists. Thus, members of the adenovirus, papovavirus, and parvovirus families are among the possible targets -- as is HIV.

At least one cdk inhibitor, a drug called flavopiridol, is currently in phase II clinical trials sponsored by the National Cancer Institute as an antitumor agent. Although these trials are investigating a different clinical goal, they have already shown the safety of flavopiridol at doses substantially higher than those thought to be necessary for antiviral treatments. For this reason, data from these trials should facilitate clinical trials of cdk inhibitors as antiviral drugs.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Novel Antiviral Drug Concept Targets Number Of Human Viruses." ScienceDaily. ScienceDaily, 25 April 2000. <www.sciencedaily.com/releases/2000/04/000424094158.htm>.
University Of Pennsylvania Medical Center. (2000, April 25). Novel Antiviral Drug Concept Targets Number Of Human Viruses. ScienceDaily. Retrieved August 2, 2014 from www.sciencedaily.com/releases/2000/04/000424094158.htm
University Of Pennsylvania Medical Center. "Novel Antiviral Drug Concept Targets Number Of Human Viruses." ScienceDaily. www.sciencedaily.com/releases/2000/04/000424094158.htm (accessed August 2, 2014).

Share This




More Health & Medicine News

Saturday, August 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Quintuplets Head Home

Texas Quintuplets Head Home

Reuters - US Online Video (Aug. 1, 2014) After four months in the hospital, the first quintuplets to be born at Baylor University Medical Center head home. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Patient Coming to U.S. for Treatment

Ebola Patient Coming to U.S. for Treatment

Reuters - US Online Video (Aug. 1, 2014) A U.S. aid worker infected with Ebola while working in West Africa will be treated in a high security ward at Emory University in Atlanta. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins