Broad-spectrum antiviral therapeutics

[tetano]

PLoS One. 2011;6(7):e22572. Epub 2011 Jul 27.
Broad-spectrum antiviral therapeutics.
Rider TH, Zook CE, Boettcher TL, Wick ST, Pancoast JS, Zusman BD.
Source

Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, Massachusetts, United States of America.
Abstract

Currently there are relatively few antiviral therapeutics, and most which do exist are highly pathogen-specific or have other disadvantages. We have developed a new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells. We have created DRACOs and shown that they are nontoxic in 11 mammalian cell types and effective against 15 different viruses, including dengue flavivirus, Amapari and Tacaribe arenaviruses, Guama bunyavirus, and H1N1 influenza. We have also demonstrated that DRACOs can rescue mice challenged with H1N1 influenza. DRACOs have the potential to be effective therapeutics or prophylactics for numerous clinical and priority viruses, due to the broad-spectrum sensitivity of the dsRNA detection domain, the potent activity of the apoptosis induction domain, and the novel direct linkage between the two which viruses have never encountered.

PMID:
21818340
[PubMed - in process]
PMCID: PMC3144912

Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/21818340

 

[Lizw]

Re: Broad-spectrum antiviral therapeutics

Anyone have more up to date info on this? I've found numerous references that it "ought to be" effective against Ebola, but no indication that it's actually being tested.

 

[JohnnyD]

Re: Broad-spectrum antiviral therapeutics

Well, I think that is the problem -- there just hasn't been much tested with ebola. The MIT drug above sounds like it is very early - I would think you'd need at least ape testing before trying it on humans.

The NIH is testing something here that sounds like it might be a broad-spectrum.

"The University of Texas Medical Branch -- is working with a $26 million award from NIH to test the possibility of combining multiple therapies, similar to the HIV-fighting "cocktail" approach. "Vaccine" and "treatment" are not interchangeable terms. A vaccine is given to prevent infection, whereas treatment generally refers to a drug given to a patient who has developed symptoms. ZMapp, given to American medical workers Nancy Writebol and Dr. Kent Brantly when they were seriously ill, is not a vaccine. "

http://www.cnn.com/2014/08/14/health/ebola-vaccine-drugs-faq/

A company I'm familiar with, Hemispherx Bipharma, has a couple of broad-spectrums in development, both of which have shown effectivness against SARS/MERS, H7N9, H5N1, etc etc. Alferon is a natural interferon and is approved for genital warts, and has an experimental Low Dose Oral form. Ampligen is a TLR-3 agonist and is experimental. Both have good human safety records.

"The new publication also notes that treatment of humans late in the course of highly lethal coronaviral infections (MERS/SARS) is unlikely to alter the clinical course as, by then, the host immune system has already likely been severely disabled. The authors therefore recommend that clinical protocols be established to evaluate systematically various therapeutic options rather than uncoordinated treatment of infected individuals as has been employed to date.

The company met with U.S. government senior biodefense/biosecurity staff on July 30, 2014, and discussed the potential application of these and other findings to highly pathogenic/lethal human viruses including Ebola virus and the ongoing outbreak in Central Africa. The potential application of these findings to the Ebola outbreak is centered on similar mechanisms of high death rates, through the viral disablement of the body's antiviral and immune defenses."

http://finance.yahoo.com/news/hemispherxs-two-drugs-ampligen-r-123000193.html

 

[Lizw]

Re: Broad-spectrum antiviral therapeutics

Yes, thanks, I'm familiar with all of those. I was just surprised to find almost no references to 'DRACO' after the initial flurry of announcements.

 

[Sharky]

Re: Broad-spectrum antiviral therapeutics

Todd Rider, the developer of DRACO, recently moved from MIT Lincoln to Draper Labs to continue his work. Definitely a very promising treatment.

http://www.prweb.com/releases/2014/01/prweb11469349.htm

 

[JohnnyD]

Re: Broad-spectrum antiviral therapeutics

http://finance.yahoo.com/news/hemispherx-biopharma-united-states-army-123000254.html

Hemispherx Biopharma and United States Army Medical Research Institute of Infectious Diseases (USAMRIID) Agree to Collaborate in Studying Alferon(R) and Ampligen(R) Against the Ebola Virus

Ebola Studies to be Conducted at USAMRIID's Laboratories at Ft. Detrick, Maryland

PHILADELPHIA, Sept. 8, 2014 (GLOBE NEWSWIRE) -- Hemispherx Biopharma, Inc. (NYSE MKT:HEB) (the "Company" or "Hemispherx"), announced that the Company and USAMRIID scientists have agreed to test Alferon(R), the only multi-species, natural alpha interferon (IFN) commercially approved in the U.S. and Ampligen(R), an experimental drug, to be evaluated against the deadly Ebola virus, which has been and remains a major focus of efforts at USAMRIID, a unit of the Department of Defense responsible for medical biological defense research.

USAMRIID reported in July of this year (http://www.usamriid.army.mil/press_releases/Randy_Final_EID_July_2014.pdf) that samples from suspected Lassa fever cases in Sierra Leone showed that about two-thirds of the patients had been exposed to other emerging diseases, and nearly nine percent tested positive for Ebola virus. The study, published in this July's edition of Emerging Infectious Diseases, demonstrates that Ebola virus has been circulating in the region since at least 2006?well before the current outbreak, which is responsible for over 1000 deaths according to the WHO. Consequently, Ebola has been and remains a major focus of efforts at USAMRIID and the Department of Defense.

Early events in Ebola virus infection influence the patient's ability to develop an effective immune response. The success of Ebola virus replication is dependent on viral inhibition of initial innate immune responses to infection. Disarming innate immune responses is a common mechanism employed by highly pathogenic human viruses that include the influenza and corona viral families. Ebola counteracts the host innate immune response by blocking the cellular production of Type I IFN.

A key component of innate immune responses is activation of the Toll-like receptors (TLRs). TLR3 activation by dsRNA is an essential response element to viral infection. Block TLR3 activation and an essential element of the innate immune response is disarmed. Ampligen, Poly Ioly C12U (rintatolimod) was designed as an IFN inducer and has demonstrated antiviral activity in a wide variety of DNA and RNA viruses in pre-clinical testing. Replenishing an Ebola patient's natural interferon with Alferon and restoring that patient's innate immune response by Ampligen's overcoming the Ebola blocking mechanisms could potentially reduce the morbidity and mortality of Ebola virus disease.

About Alferon(R) N

Alferon(R) N is the only natural source, multi-species alpha interferon currently approved for sale in the U.S. Alferon(R) N is approved in the U.S. only for the treatment of refractory or recurring external genital warts caused by human papilloma virus in patients 18 years of age or older.

About Ampligen(R)

Ampligen(R), an experimental therapeutic, is a new class of specifically-configured ribonucleic acid (RNA) compounds targeted as potential treatment of diseases with immunologic defects and/or viral causation.

 

[Laidback Al]

Re: Broad-spectrum antiviral therapeutics

It is important to note that the information in the above post is a news release from Hemispherx Biopharma and should be interpreted with caution. Here is the associated disclosure information attached to the release.

Disclosure Notice

Information contained in this news release, other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, changes in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company's filings with the Securities and Exchange Commission. The final results of these efforts and/or any other activities could vary materially from Hemispherx's expectations. In vitro experiments are not necessarily predictive of clinical outcome and no representations are made that any products described in this release will be ultimately determined safe and effective in the prevention and/or treatment of the Ebola virus. Moreover, it would take time, testing and funds to obtain approval of any such product and there are no assurances that a commercial approval for treatment of the Ebola virus can be obtained.

Forward-Looking Statements

To the extent that statements in this press release are not strictly historical, all such statements are forward-looking, and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "potential," "potentially," "possible," and similar expressions are intended to identify forward-looking statements. The inclusion of forward-looking statements should not be regarded as a representation by Hemispherx that any of its plans will be achieved. These forward-looking statements are neither promises nor guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond Hemispherx's control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. Examples of such risks and uncertainties include those set forth in the Disclosure Notice, above, as well as the risks described in Hemispherx's filings with the Securities and Exchange Commission, including the most recent reports on Forms 10-K, 10-Q and 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Hemispherx undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise revise or update this release to reflect events or circumstances after the date hereof.