Featured Research

from universities, journals, and other organizations

Compound stymies polyomaviruses in lab tests

Date:
November 13, 2013
Source:
Brown University
Summary:
There is no approved medicine to treat polyomaviruses, which afflict those with weakened immune systems, but scientists have found that a chemical compound called Retro-2 is able to significantly reduce the infectivity and spread of the viruses in lab cell cultures. Now they are working to improve it further.

Other substances can control the polyoma virus only if they were administered prior to infection. In cell culture studies, Retro-2 appears to control the infectivity and spread of polyomavirus even when the virus is already established.
Credit: Atwood lab/Brown University

A team of scientists reports that a small-molecule compound showed significant success in controlling the infectivity and spread of three polyomaviruses in human cell cultures. To date there has been no medicine approved to treat such viruses, which prey on transplant recipients, people with HIV, and others whose immune systems have been weakened.

Related Articles


The compound, known by the abbreviated name "Retro-2," was able to protect the vast majority of cells in cultures when it was administered even after infection began. According to results published in the journal mBio, 12 days of treatment with Retro-2 kept 90.5 percent of cells free from JC polyomavirus, 89 percent of cells clear of the BK polyomavirus, and 84 percent of cells protected from the SV40 polyomavirus. Infection rates and virus production were much higher among cells in cultures that were similarly infected but left untreated as controls.

That the compound gained the upper hand on viruses that had a head start is a key advance, said Brown University biologist Walter Atwood, corresponding author of the paper. Other substances have defeated the viruses only if they were used to pre-treat cells before any infection.

"But that's not reality," Atwood said. "The reality is that someone is already infected with the virus. Whenever in the past we first infected the cells with the virus and then came in with the drug, we've never been successful in being able to stop the spread of the virus. This drug is successful at that."

Brown University has a patent filed on the use of the compound against pathogen infections. The research also involved a team of scientists at Yale University led by Daniel DiMaio.

An 'ER' medicine

Retro-2 appears to work by blocking the ability of polyomaviruses to sneak around host cells by hijacking the intracellular protein transportation hub: the endoplasmic reticulum (ER).

Christian Nelson, a Brown postdoctoral researcher currently visiting at Yale, first thought to study Retro-2 after reading a 2010 paper in Cell showing that it blocks certain toxins, including ricin, from working through the ER. Ricin and polyomaviruses have been thought to operate similarly. The compound also did not appear to be toxic to the mice in that study.

"There are a lot of viruses that use these trafficking mechanisms," Atwood said.

So the team bought some Retro-2 from Chembridge, a company that makes vast libraries of small-molecule compounds for scientists to study, and pitted it against the polyomaviruses.

The researchers tested it in several ways, including with both kidney cells and brain cells because those are the tissues in the body where they can cause disease. Retro-2 appeared effective in protecting the various cells, as long as it was present within several hours of infection.

"When this causes disease in people, there's progressively more and more cells infected," Nelson said. "If we can identify infection early, a treatment could help to stop that progression."

Improving the chemistry

Atwood and Nelson acknowledge that they aren't yet sure exactly how Retro-2 blocks the viruses in the ER, but thanks to a team of collaborating chemists, they do know what chemical structure makes the drug effective.

Brown chemistry professors Jason Sello and Paul Williard and graduate student Daniel Carney studied the compound's chemical structure. In efforts to prepare Retro-2, Sello and Carney found that the last step in the synthesis yielded not only the reported structure but also a form called a dihydroquinazolinone (DHQ). The DHQ was the apparent result of a "cyclizing" reaction of Retro-2 that gives it a different chemical structure.

Further experiments identified the exact structure of the DHQ form and showed that it was the form that matched what Atwood and Nelson had found to be effective in the lab.

This detailed understanding of the compound is helping Sello and his team improve the drug further.

"A critical part of any drug development program is the unambiguous assignment of the structure of the lead compound," Sello said. "With knowledge of the Retro-2 structure, we have been rationally preparing analogs that have improved pharmacological properties."


Story Source:

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


Journal Reference:

  1. C. D. S. Nelson, D. W. Carney, A. Derdowski, A. Lipovsky, G. V. Gee, B. O'Hara, P. Williard, D. DiMaio, J. K. Sello, W. J. Atwood. A Retrograde Trafficking Inhibitor of Ricin and Shiga-Like Toxins Inhibits Infection of Cells by Human and Monkey Polyomaviruses. mBio, 2013; 4 (6): e00729-13 DOI: 10.1128/mBio.00729-13

Cite This Page:

Brown University. "Compound stymies polyomaviruses in lab tests." ScienceDaily. ScienceDaily, 13 November 2013. <www.sciencedaily.com/releases/2013/11/131113130031.htm>.
Brown University. (2013, November 13). Compound stymies polyomaviruses in lab tests. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2013/11/131113130031.htm
Brown University. "Compound stymies polyomaviruses in lab tests." ScienceDaily. www.sciencedaily.com/releases/2013/11/131113130031.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Stray Dog Follows Adventure Racing Team for 6-Day Endurance Race

Stray Dog Follows Adventure Racing Team for 6-Day Endurance Race

Buzz60 (Nov. 24, 2014) A Swedish Adventure racing team travels to try and win a world title, but comes home with something way better: a stray dog that joined the team for much of the grueling 430-mile race. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Terrifying Black Seadevil Fish Captured on First-of-Its Kind Video

Terrifying Black Seadevil Fish Captured on First-of-Its Kind Video

Buzz60 (Nov. 24, 2014) An aquarium captures a first-of-its kind video of a notoriously camera-shy fish that’s also not so camera-friendly. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Red Panda Cubs Explore the Bratislava Zoo

Red Panda Cubs Explore the Bratislava Zoo

AFP (Nov. 24, 2014) Four-month old Red Panda twins Pim and Pam still rely on their mother for breast milk at the Bratislava Zoo in Slovakia, but the precocious cubs have begun to branch out to solid foods, as well. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. 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


Plants & Animals

Earth & Climate

Fossils & Ruins

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