TWiV 253: I don’t know anything about sorghum

On episode #253 of the science show This Week in Virology, the complete TWiV team reads questions and comments from listeners about systemic antiviral responses, wild type poliovirus in Israel, Turkish scientists, viral symbiotes, and much more.

You can find TWiV #253 at www.microbe.tv/twiv.

TWiV 235: Live in Edmonton, eh?

Episode #235 of the science show This Week in Virology was recorded before an audience at the 2nd Li Ka Shing Institute of Virology Symposium at the University of Alberta, where they spoke with Dave, Stan, and Lorne about their work on poxvirus vaccines and recombination, an enveloped picornavirus, antivirals against hepatitis B and C viruses, and supporting virology research in Alberta.

You can find TWiV #235 at www.microbe.tv/twiv.

TWiP 30: Global infectious disease control with Charles Knirsch

Charles KnirschHosts: Vincent Racaniello and Dickson Despommier

Vincent and Dickson have a broad-ranging conversation with Charles Knirsch of Pfizer, Inc. about how public-private partnerships can function to control and eliminate infectious diseases.

Click the arrow above to play, or right-click to download TWiP #30 (61 MB .mp3, 85 minutes).

Links for this episode:

Contact

Send your questions and comments (email or mp3 file) to twip@microbe.tv.

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TWiV 146: Draco’s potion

dracoHosts: Vincent RacanielloRich Condit, and Abbie Smith

Vincent, Rich, and Abbie review a broad spectrum antiviral protein, and selective pressure applied by a failed HIV-1 vaccine.

Click the arrow above to play, or right-click to download TWiV 146 (78 MB .mp3, 107 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Vincent – Hypothetical Risk: Cambridge City Council’s Hearings on Recombinant DNA Research
Rich –
Z Corporation 3-D printer (YouTube)

Listener Pick of the Week

JimDo-it-yourself DNA extraction (Citizen Scientist Quarterly)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 130: Rhino tracking, wrestling pox, and HCV in the crosshairs

organ culture hrv cHosts: Vincent Racaniello, Alan Dove, and Rich Condit

Vincent, Alan, and Rich discuss growth in culture of newly identified rhinovirus C, vaccinia transmission among wrestlers and martial artists, and results of phase III clinical trial of boceprevir, a new inhibitor of hepatitis C virus replication.

Click the arrow above to play, or right-click to download TWiV #130 (45 MB .mp3, 93 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Rich – Rock-paper-scissors vs computer (thanks, Megan!)
Alan –
WebCite
Vincent – Edward Jenner Museum (EID)

Listener Pick of the Week

Derek Tolly  – A Paralyzing Fear: The Story of Polio in America (IMDb)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 121: Huskies go viral

viral huskiesHosts: Vincent Racaniello, Michael Katze, Michael Gale, Deborah Fuller, and Shawn Iadonato

Episode #121 of the podcast This Week in Virology is a conversation about careers in virology, systems biology, innate immunity, and antiviral research recorded at the University of Washington in Seattle.

Click the arrow above to play, or right-click to download TWiV #121 (65 MB .mp3, 90 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:


Weekly Science Picks

Michael K – Pasteur Museum
Deborah – Undaunted Courage by Stephen Ambros
Michael G – The Eighth Day of Creation by Horace Freeland Judson
Vincent –
The Emperor of All Maladies by Siddhartha Mukherjee

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 99: ICAAC Boston 2010

Host: Vincent Racaniello

Vincent tours the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Boston, speaking with exhibitors and visitors, including Professors Derek Smith, Michael Schmidt, Frederick Hayden, and Myra McClure.

Many thanks to Chris Condayan and Ray Ortega of the American Society for Microbiology for recording and editing this episode.

Click the arrow above to play, or right-click to download TWiV #99 (45 MB .mp3, 62 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

TWiV 92: Live at ASV in Bozeman

Hosts: Vincent Racaniello, Rich Condit, Karla Kirkegaard, and Marilyn Roosinck

On episode #92 of the podcast This Week in Virology, Vincent, Rich, Karla, and Marilyn recorded TWiV at the 29th Annual Meeting of the American Society for Virology in Bozeman, where they discussed plant viruses and how they make plants resistant to adverse conditions, and identification of dominant negative drug targets.

Click the arrow above to play, or right-click to download TWiV #92 (42 MB .mp3, 57 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

Weekly Science Picks

Marilyn – Viruses in the faecal microbiota of monozygotic twins and their mothers (Nature)
Rich –
The Known Universe by the American Museum of Natural History
Vincent – The Red Queen by Matt Ridley (thanks, Jesper!)

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.

A new target for hepatitis C virus

When infection with hepatitis C virus goes from acute to chronic, severe liver disease may occur which requires organ transplantation. Nearly 200 million people are chronically infected with HCV, necessitating approaches to preventing and treating infections. No HCV vaccine is available, and current antiviral therapy consists of administration of interferon plus ribavirin, a combination that is effective about half the time and is associated with undesirable side effects. New antiviral compounds that target a viral protease and RNA polymerase are currently in clinical trials may eventually reach the market. But our experience with HIV-1 has shown that combinations of three drugs are the most effective for derailing the emergences of drug resistant viruses. The third target for HCV could be NS5A, a viral protein without a known function.

To identify new inhibitors of HCV, a chemical library of one million compounds was screened for the ability to inhibit viral replication in cell culture. The active compound were then subjected to a second screen to eliminate inhibitors of known viral enzymes: the viral protease, RNA polymerase, and helicase. One of the remaining inhibitors was further refined chemically until a very potent derivative was obtained. This molecule, called BMS-790052, has a 50% inhibitory concentration in the picomolar range, and inhibits all the viral genotypes tested. It is the most powerful inhibitor of HCV discovered.

The compound was tested for safety and bioavailability in various animal species. After oral administration, the compound was found in plasma and liver, despite a molecular mass of over 700 daltons. Six different levels of the compound were tested in HCV infected individuals. No adverse effects were reported, and the highest amount administered reduced viral levels in the blood 2,000 fold after one day. These results are promising, but larger trials will now be needed to further confirm the safety and efficacy of the drug.

What is the target of BMS-790052? Two lines of evidence suggest that the compound inhibits the viral protein NS5A. The drug appears to bind NS5A, and viruses resistant to the drug have amino acid changes in this protein. Although NS5A is known to be required for viral replication, its precise function is not known. Because NS5A does not have an easily assayable enzymatic function, it has not previously been a target of drug discovery. The identification of a compound that inhibits NS5A function is an important step forward in HCV drug development. The general approach used to discover BMS-790052 should be useful in identifying inhibitors of other viral proteins that do not have well defined and measurable activities.

I discussed this paper on Futures in Biotech episode #60. If you would like to listen only to the conversation about BMS-790052, download this mp3 file, or listen to the discussion below.

[audio:http://www.virology.ws/fib60.mp3 | titles=FIB 60]

Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, Serrano-Wu MH, Langley DR, Sun JH, O’Boyle DR 2nd, Lemm JA, Wang C, Knipe JO, Chien C, Colonno RJ, Grasela DM, Meanwell NA, & Hamann LG (2010). Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature, 465 (7294), 96-100 PMID: 20410884

TWiV 85: Hepatitis C virus with Professor Michael Gale

Hosts: Vincent Racaniello and Michael Gale

On episode 85 of the podcast This Week in Virology, Vincent and Michael Gale discuss the origin, pathogenesis, prevention, of hepatitis C virus, and how it evades innate immune responses.

This episode is sponsored by Data Robotics Inc. Use the promotion code TWIVPOD to receive $75-$500 off a Drobo.

Click the arrow above to play, or right-click to download TWiV #85 (40 MB .mp3, 56 minutes)

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, or by email, or listen on your mobile device with Stitcher Radio.

Links for this episode:

  • The Gale Laboratory at the University of Washington
  • Incredible view from the Gale laboratory (jpg)
  • Evasion and disruption of innate immune signalling by hepatitis C and West Nile viruses (review)
  • New potent HCV inhibitor
  • HCV virion and genome structures at ViralZone

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.