Featured Research

from universities, journals, and other organizations

Drug against AIDS could be effective against herpesvirus

Date:
September 24, 2010
Source:
Institute for Research in Biomedicine-IRB
Summary:
Scientists have shown that raltegravir, the drug approved in 2007 for the treatment of AIDS that is sold by Merck under the name Isentress, cancels the function of an essential protein for the replication of one kind of herpes virus. This study is the first step towards the development of a drug against the entire herpesvirus family.

Scientists at the Institute for Research in Biomedicine (IRB Barcelona) headed by the coordinator of the Structural and Computational Biology Programme, Miquel Coll, have published a new study that demonstrates that raltegravir, the drug approved in 2007 for the treatment of AIDS that is sold by Merck under the name Isentress, cancels the function of an essential protein for the replication of one kind of herpes virus. This study, published in the journal Proceedings of the National Academies of Sciences (PNAS), is the first step towards the development of a drug against the entire herpesvirus family.

Related Articles


"These results have a clear medical impact for three reasons," explains Miquel Coll, also a CSIC research professor. "First, humans do not have the viral protein that is affected, thus this would allow a highly specific drug that does not show the secondary effects that other drugs may have. Second, the inhibitor is not toxic for humans when administered at therapeutic concentrations because it is already on the market and thus toxicity tests are facilitated; and third, we have data that indicate that all herpes viruses have this protein. Therefore, it could be a valid target against all Herpesviridae."

Herpesviruses include pathogens such as herpes simplex 1 and 2, the virus that causes chickenpox otherwise known as zoster virus, the Epstein-Barr virus -associated with several types of cancer -, the roseola virus, the cytomegalovirus and the herpes virus associated with Kaposi sarcoma -in AIDS patients -. The human cytomegalovirus (HCMV), on which the study was performed, causes neurological defects in 1% of neonates in developed countries. It also produces retinitis that deteriorates into blindness in 25% of subjects with AIDS, defects in the brains and central nervous systems of young adults, inflammation of the colon -also in those with AIDS -, mononucleosis and serious diseases of the throat. Although 90% of adults carry HCMV, this virus is opportunistic, acting in people with weakened immune systems such as in cancer and AIDS patients, recipients of organ transplants and neonates.

Blocking viral replication

To replicate, the herpes virus enters the nucleus of a cell where it uses the cell machinery to copy its DNA several times into a single large chain. Once this copy has been made, acts a complex called terminase, formed by three protein subunits. The terminase cuts the new DNA into small fragments, the size of a single viral genome, and introduces these into empty shells (capsids) that have developed in the cell nucleus. Then, the new viruses leave the cell to continue infection. The researchers resolved the 3D structure of one part of the terminase and when they observed that it resembled the integrase of the AIDS virus, for which drugs are available, they tested it against the herpes virus protein. Thus they discovered that raltegravir acts on the subunit UL89 of the terminase and cancels the scissor function, which is required for viral replication.

The assays were performed directly on the protein in test tubes. "Now we must do the assays on whole infected cells, improve the effect of the drug and validate that it is also effective for other kinds of herpes viruses," explains Miquel Coll, whose lab has patented this second application for raltegravir. To resolve the 3D structure of the target protein, the scientists have used a state-of-the-art high-performance protein expression technique, with the collaboration with Darren Hart's group at EMBL in Grenoble, where 18,000 clones or different fragments of the protein have been tested. They have also used the Grenoble synchrotron to obtain the structural data. The study has lasted five years and forms part of the European project SPINE-2 complexes.


Story Source:

The above story is based on materials provided by Institute for Research in Biomedicine-IRB. Note: Materials may be edited for content and length.


Journal Reference:

  1. M. Nadal, P. J. Mas, A. G. Blanco, C. Arnan, M. Sola, D. J. Hart, M. Coll. Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain. Proceedings of the National Academy of Sciences, 2010; 107 (37): 16078 DOI: 10.1073/pnas.1007144107

Cite This Page:

Institute for Research in Biomedicine-IRB. "Drug against AIDS could be effective against herpesvirus." ScienceDaily. ScienceDaily, 24 September 2010. <www.sciencedaily.com/releases/2010/09/100923081859.htm>.
Institute for Research in Biomedicine-IRB. (2010, September 24). Drug against AIDS could be effective against herpesvirus. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2010/09/100923081859.htm
Institute for Research in Biomedicine-IRB. "Drug against AIDS could be effective against herpesvirus." ScienceDaily. www.sciencedaily.com/releases/2010/09/100923081859.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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