Innovative drug screening technique yields potential flu treatment Drug-like compound hits a vulnerable spot on multiple strains of the flu virus.
July 21, 2020
LA JOLLA, CA Scientists from Scripps Research have used a powerful new drug screening method to find a compound that neutralizes multiple strains of influenza virus.
The potential new drug lead compound, described in the Proceedings of the National Academy of Sciences, hits a vulnerable site on flu viruses the so-called hemagglutinin (HA) stem whose important role in infecting cells means that it does not vary much from one flu strain to the next.
Certain rare human antibodies can neutralize a broad variety of flu strains by binding to this same HA stem site, but all of the currently approved antiviral flu drugs attack other sites on the virus.
With this compound, we can start to attack influenza virus in a way that hasn't been done before with existing flu drugs, and at an early stage of the infection process, says the studys senior author Dennis Wolan, PhD, an associate professor in the Department of Molecular Medicine at Scripps Research.
The study was a collaboration between Wolan's lab and the lab of Ian Wilson, DPhil, Hansen Professor of Structural Biology and Chair of the Department of Integrative Structural and Computational Biology at Scripps Research.
This is a good step forward in an ongoing effort to find new templates and lead compounds to design drugs that inhibit the influenza virus HA protein, Wilson says.
There's a strong need for new drug treatments for influenza. Flu viruses kill more than 50,000 people in the United States every year, and occasionally as in the 1918 Spanish flu cause pandemics with death tolls in the millions. Existing flu drugs such as Tamiflu (oseltamivir) can be useful in preventing or in treating severe flu cases, but these drugs target sites on flu viruses where the viruses can mutate relatively easily to become drug-resistant.
Existing seasonal flu vaccines also are useful, but have to be updated annually and don't cover emerging viruses or potential pandemic threats, such as bird flu, and often do not work well in elderly people and others with weakened immune systems.
In recent years, Wilson's lab and others have studied antibodies isolated from flu patients that can neutralize a broad range of influenza strains. Some of the most potent of these broadly neutralizing antibodies (bnAbs) attack the HA stem. HA proteins stud the surface of a flu virus particle and can attach to certain receptors on cells in the respiratory tract.
Once attached, the HA stem structure normally alters its shape to enable the virus to fuse with the host cell's outer membrane, thus enabling entry into the cell. Antibodies that bind to the HA stem can block that HA shape-shift from happening and thus prevent viral entry.
The researchers for the new study developed a method for finding potential drug molecules that hit this vulnerable site in the same way that broadly neutralizing antibodies do.
The new method makes use of a peptide called P7, which was originally designed at Janssen Pharmaceutica, to mimic key portions of stem-binding broadly neutralizing antibodies. The method allows researchers to test in a relatively quick, automated and low-cost way a large collection of thousands of sample compounds, to find any that compete with P7 to bind to the same tightly defined portion of the HA stem.
Using the new method, the team screened about 72,000 compounds and found one, F0045(S), that powerfully neutralizes multiple H1N1 human influenza strains in vitro as well as multiple H5N1 bird flu strains, which rarely infect humans but carry a high mortality rate when they do. Wilson's lab used X-ray crystallography to confirm, at atomic resolution, that F0045(S) binds to the influenza HA stem much in the same way as broadly neutralizing antibodies.
F0045(S) on the whole appears to work against the largest family of influenza A HA subtypes, the group 1 HAs, which contain H1N1 human influenza as well as H5N1 and other virus subtypes. Group 2 HAs, which include H3N2 human influenza viruses, and HAs in a separate set of flu viruses called Influenza B viruses, have slightly different structures and so for these, the researchers expect to have to modify F0045(S) significantly, or screen for new stem-targeting compounds.
Possibly we would end up with a cocktail of several drug compounds targeting different families of HA proteins to cover most or all flu strains, Wolan says.
The researchers are now using chemistry techniques to modify F0045(S) to improve its stem-binding affinity and general drug properties, and they expect to continue developing it and related compounds to search for new leads that could be developed into novel flu treatments.
An Influenza A Hemagglutinin Small-Molecule Fusion Inhibitor Identified by a New High-Throughput Fluorescence Polarization Screen was authored by Yao Yao, Rameshwar Kadam, Chang-Chun Lee, Jordan Woehl, Nicholas Wu, Xueyong Zhu, Seiya Kitamura, Ian Wilson, and Dennis Wolan, all of Scripps Research.
The work was supported by the National Institutes of Health (R56 AI127371, K99 AI39445) and the Bill and Melinda Gates Foundation (OPP1170236).
Infectious Diseases Wolan, Dennis Wilson, Ian
Most recent headlines
04/08/2024
Dalet, a leading technology and service provider for media-rich organizations, is excited to announce Santiago Solanas as its new Chief Executive Officer (CEO)....
03/06/2024
Dalet, a leading technology and service provider for media-rich organizations, a...
28/04/2024
Mediahaus delivers the first SRT live-streaming sports production over 5G with U...
27/04/2024
On April 26, L3Harris Chair and CEO Christopher E. Kubasik joined CNBC's Mor...
27/04/2024
PORTLAND, Oregon Audinate Group Limited, the developer of the Dante AV-over-IP solution, announced significant new additions to Dante Connect, its cloud-based D...
27/04/2024
TORONTO Bell Media has launched 10 English and French-language FAST channels featuring entertainment, factual, news, and sports programming. The new free stream...
27/04/2024
An extensive new analysis of the news segments in the broadcast evening news programs of ABC, CBS, NBC and PBS has found that broadcasters devoted most of their...
27/04/2024
GERMANTOWN, Md. EchoStar's Hughes Network Systems has opened a new manufacturing facility and private 5G incubation center in Germantown, Maryland....
27/04/2024
Harry Pappas, one of three brothers who founded Pappas Telecasting Companies in 1971, died April 24. He was 78 years old....
27/04/2024
ATLANTA and LONDON Mexican telecommunications and broadcast company Televisa has selected Synamedia for an overhaul of its broadcast distribution....
27/04/2024
Participate in the Survey - The Impact of AI on Media and the Creative Industry
Pascal Wagner April 26, 2024
0 Comments
By participating in this surve...
27/04/2024
SDVI Rally Access Workstation Earns Two Top Awards at 2024 NAB Show
Brie Clayton April 26, 2024
0 Comments
SDVI, the leading platform provider for clo...
27/04/2024
Berklee's Music and Health Institute Launches Community Health Musician Cert...
27/04/2024
Charter Communications reported higher first-quarter profits despite continued cord-cutting and competition for broadband customers....
27/04/2024
Two environmentally-focused groups are partnering to engage the unscripted TV world in finding better ways to address climate change. Reality of Change is an ec...
27/04/2024
Sarah Garcia has been promoted to weekend anchor at KTLM McAllen, Texas, known as Telemundo 40. Starting April 27, she will anchor Noticias Telemundo 40 weekend...
27/04/2024
CBS Sports said it launched a new 24-hour free, ad supported streaming television (FAST) channel devoted to the UEFA Champions League....
27/04/2024
Comcast chairman and CEO Brian Roberts received $35.4 million in compensation in 2023, up 11% from the previous year, according to a proxy statement filed by th...
27/04/2024
Art Happens Here With John Lithgow, which sees the actor study dance, ceramics, silk-screen printing and vocal jazz with students in Los Angeles, debuts on PBS ...
27/04/2024
Remember Leave It to Beaver? Bewitched? Dragnet? When cable ratings were rising?...
27/04/2024
Next up for the weekend binge at Catchy Comedy is Gomer Pyle, U.S.M.C. Every weekend, Catchy Comedy features The Catchy Binge, a marathon of a classic sitcom....
26/04/2024
Sundance Film Festival CDMX 2024 kicks-off today with screenings in 5 theaters in Mexico City and the opening-night film, FRIDA, directed by Carla Guti rrez...
26/04/2024
[Editor's Note: This interview is part of a larger feature about the women d...
26/04/2024
Once again this year, SGL Carbon opened its doors to interested children and young people. On the occasion of the German Girls and Boys Day, which took place on...
26/04/2024
Orders1 of $5.5 billion; book-to-bill of 1.06x
Revenue of $5.2 billion, up 17%,...
26/04/2024
Five Considerations For Communications Modernization In The 21st Century
In the digital-enabled battlespace, the Joint Force needs to shoot, move and communica...
26/04/2024
CBS Sports has launched Champions League as a new, 24-hour streaming channel that will serve as the year-round destination for nonstop highlights of the UEFA ...
26/04/2024
Despite tough competition in the streaming space, Roku reported solid results in Q1 2024, beating revenue expectations, with total net revenue up 19% YoY to $88...
26/04/2024
LONDON AND TORONTO Pinewood Toronto Studios has appointed Sarah Farrell as general manager of the Studios in downtown Toronto....
26/04/2024
Quantum to Offer Advanced Filesharing Technology and Performance in StorNext and...
26/04/2024
FilmLight Colour Awards welcomes 2024 entries and introduces new Emerging Talen...
26/04/2024
Picture Shop Announces Chris Evans as Head of Unscripted
Brie Clayton April 26, 2024
0 Comments
Picture Shop announced Chris Evans will lead Unscripte...
26/04/2024
Participate in a Survey - The Impact of AI on Media and the Creative Industry
Pascal Wagner April 26, 2024
0 Comments
By participating in this survey,...
26/04/2024
Toy maker Mattel said it is working with Samsung to launch its first free ad-supported streaming television (FAST) channels later this year....
26/04/2024
Trusted Media Brands (TMB) said it named Marty Moe as president....
26/04/2024
Ron Howard is the director on Jim Henson Idea Man, a documentary that premieres on Disney Plus May 31. Henson of course created Kermit the Frog, Miss Piggy, Big...
26/04/2024
The ice continues to melt under the regional sports network business as the Seattle Kraken of the National Hockey League have made a long-term deal to broadcast...
26/04/2024
Heading into the upfronts, Warner Bros. Discovery said it launched Olli, a first-party data platform advertiser can use for converged, targeted advertising camp...
26/04/2024
CBS has renewed the drama The Equalizer, which will see season five on in 2024-2025. Queen Latifah stars....
26/04/2024
The CW has entered into an exclusive multiyear broadcast partnership for the Miss USA Pageant and the Miss Teen USA Pageant. The 73rd Miss USA Pageant will air ...
26/04/2024
Fuse Media isn't mincing words in a campaign urging its young viewers to register and participate in the 2024 elections....
26/04/2024
Dead Boy Detectives, a series from Neil Gaiman about a detective agency staffed by ghosts, debuts on Netflix April 25. George Rexstrew and Jayden Revri are in t...
26/04/2024
The Story Collective has gradually repurposed the former Mortlake Brewery to include production offices, workshops and sound stages
By Matthew Corrigan
Publi...
26/04/2024
Perkett joins the company following a 25 year career in product management, product marketing, engineering and user experience (UX) across multiple industries
...
26/04/2024
Teradek, the industry leader in wireless video transmitters and receivers, announced today the launch of new Bolt 6 LT 750 and Bolt 6 Monitor Module 750 RX with...
26/04/2024
NEW YORK Amagi has appointed Richard Perkett chief product officer (CPO)....
26/04/2024
WASHINGTON, D.C. The National Association of Broadcasters (NAB) has announced the results of the 2024 NAB Radio and Television Board of Directors elections. The...
26/04/2024
EL SEGUNDO, Calif. & NEW YORK Mattel has announced a deal to launch its first three 24/7 free ad supported streaming (FAST) channels on Samsung TV Plus, Samsung...
26/04/2024
PORTLAND, Maine Viewers here can now receive the NextGen TV signals of five local stations with the launch of ATSC 3.0 service from host station WPFO, which is ...
Innovative drug screening technique yields potential flu treatment Drug-like compound hits a vulnerable spot on multiple strains of the flu virus.
