Lectin/BanLec/Bananas/Scientists identify chemical in bananas as potent inhibitor of HIV infection | NNVC.OB Message Board Posts

From IV

[SNIP]

A potent and potential ligand for our HIVCide - lectin from bananas which attracts HIV and attaches to it preventing any cell entry:

Scientists identify chemical in bananas as potent inhibitor of HIV infection

March 15, 2010

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This is a 3-D structure of BanLec, a chemical isolated from bananas identified as a potent new inhibitor of HIV infection. Credit: University of Michigan Medical School

A potent new inhibitor of HIV, derived from bananas, may open the door to new treatments to prevent sexual transmission of HIV, according to a University of Michigan Medical School study published this week.

Scientists have an emerging interest in lectins, naturally occurring chemicals in plants, because of their ability to halt the chain of reaction that leads to a variety of infections.

In laboratory tests, BanLec, the lectin found in bananas, was as potent as two current anti-HIV drugs. Based on the findings published March 19 in the Journal of Biological Chemistry, BanLec may become a less expensive new component of applied vaginal microbicides, researchers say.

Tailor-Made HIV/AIDS Treatment Closer to Reality

ScienceDaily (Nov. 26, 2009) — An innovative treatment for HIV patients developed by McGill University Health Centre researchers has passed its first clinical trial with flying colours. The new approach is an immunotherapy customized for each individual patient, and was developed by Dr. J-P. Routy from the Research Institute of the MUHC in collaboration with Dr. R. Sékaly from the Université de Montréal. "This is a vaccine made for the individual patient -- an "haute couture" therapy, instead of an off-the-rack treatment" said Dr Routy.

By "priming" the immune system, as with a vaccine, to fight the specific strain of HIV/AIDS infecting a given patient, the scientists believe they have developed a therapy that shows immense promise and could be an even more effective weapon against the virus than the anti-retroviral cocktails currently in use. The results of the first-stage clinical trials, which tested the therapy in conjunction with anti-retroviral drugs, were published recently in Clinical Immunology. Phase 2 of the clinical trial, which is nearly complete, is testing the therapy's efficacy on its own at 8 different sites in Canada.

The new therapy uses dendritic cells which are removed from each HIV-infected patient and subsequently multiplied in-vitro. Dendritic cells present material from invading viruses on their surface, allowing the rest of the immune system to identify and attack the invaders. "They are the "grand conductors" of the immune response," explains Dr Routy. "With them, you push the immune system, in all its functions, at the same time." In the current trial, dendritic cells were exposed to a sample of HIV RNA (ribonucleic acid) specific to the patient involved. This exposure encouraged the cells to develop defences specific to that viral strain. The modified cells -- called AGS-004 -- were then injected back into the patients.

Not only were there few reported side-effects from the AGS-004, but the researchers also measured increased levels of CD8-lymphocytes in the patients -- the "attack" cells of the human immune system that the treatment is intended to mobilize, thus confirming that the intervention was targeted and controlled.

By boosting the immune system in this way, Routy hopes to develop an HIV/AIDS treatment that will require fewer injections and less long-term toxicity for patients than antriretrovirals.

Dr. Jean-Pierre Routy is a practitioner in the Division of Hematology at the MUHC as well as a researcher in the Infection and Immunity Axis at the Research Institute of the MUHC. He is also an Associate Professor of Hematology at McGill University in addition to a senior clinical researcher with the Fonds de la Recherche en Santé du Québec (FRSQ).

This study was funded by a grant from the Canadian Network for Vaccines and Immunotherapeutics (CANVAC), the Canadian HIV Trials Network (CTN), the National Institutes of Health (NIH) and Argos Therapeutics.

This article was co-authored by Rafick-Pierre Sékaly, Université de Montréal, Mohamed-Rachid Boulassel of the McGill University Health Centre (MUHC), Bader Yassine-Diab and Oleg Yegorov of the Université de Montréal and Centre Hospitalier de l'Université de Montréal (CHUM), Lothar Finke, Don Healey, Renu Jain, Tamara Monesmith ,Charles Nicolette and Irina Tcherepanova of Argos Therapeutics, In, Durham, USA.

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Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses

Science 27 March 2009:
Vol. 323. no. 5922, pp. 1743 - 1747
DOI: 10.1126/science.1167525

Reports

Wolfgang Hübner,¹ Gregory P. McNerney,³ Ping Chen,¹ Benjamin M. Dale,¹ Ronald E. Gordon,² Frank Y. S. Chuang,³ Xiao-Dong Li,⁴ David M. Asmuth,⁴ Thomas Huser,^3,4 Benjamin K. Chen^1*

The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.

¹ Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
² Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
³ NSF Center for Biophotonics Science and Technology, University of California Davis (UCD), Sacramento, CA 95817, USA.
⁴ Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA 95817, USA.

^* To whom correspondence should be addressed. E-mail: ben.chen@mssm.edu

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• An interesting informative presentation with numerous videos:
  

[SNIP]
It turns out that HIV doesn't work like this (mostly). In fact, it operates more much more sneakily -- like special forces -- viral ninjas, if you will. Instead of spreading out in the blood, HIV viruses transfer between infected cells through a structure called a virological synapse. (To be accurate, HIV does infect cells in a cell-free form -- this is discussed in the Introduction of the paper. However, cell-to-cell transfer of HIV is up to a thousand times more efficient and inhibiting it inhibits viral replication.)

http://scienceblogs.com/purepedantry/2009/03/watch_hiv_t-cell_transfer_live.php

Waking up dormant HIV

March 16th, 2009

HAART (highly active anti-retroviral therapy) has emerged as an extremely effective HIV treatment that keeps virus levels almost undetectable; however, HAART can never truly eradicate the virus as some HIV always remains dormant in cells. But, a chemical called suberoylanilide hydroxamic acid (SAHA), recently approved as a leukemia drug, has now been shown to 'turn on' latent HIV, making it an attractive candidate to weed out the hidden virus that HAART misses.

Matija Peterlin at UCSF and colleagues had previously identified another chemical called HMBA that could activate latent HIV, but the risk of several toxic side effects made HMBA clinically non-viable. However, the chemically similar SAHA had received FDA approval, making it a potentially safer alternate.

So, the researchers examined whether SAHA had any effect on HIV latency. They found that SAHA could indeed stimulate latent HIV to begin replicating, which exposes the infected cell to HAART drugs. SAHA could activate HIV in both laboratory cells as well as from blood samples taken from HIV patients on antiretroviral therapy. Importantly, this successful activation was achieved using clinical doses of SAHA, suggesting toxicity will not be a problem.

More information: This study appeared in the March 13 issue of Journal of Biological Chemistry, "Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells" by Xavier Contreras, Marc Schwenker, Chin-Shih Chen, Joseph M. McCune, Steven G. Deeks, Jeffrey Martin, and B. Matija Peterlin

Article link: http://www.jbc.org/cgi/content/full/284/11/6782

Source: American Society for Biochemistry and Molecular Biology

http://www.physorg.com/news156424517.html

Suberoylanilide Hydroxamic Acid Reactivates HIV from Latently Infected Cells^*

Originally published In Press as doi:10.1074/jbc.M807898200 on January 9, 2009 J. Biol. Chem., Vol. 284, Issue 11, 6782-6789, March 13, 2009

Xavier Contreras¹, Marc Schweneker², Ching-Shih Chen^¶, Joseph M. McCune³, Steven G. Deeks^||, Jeffrey Martin^**, and B. Matija Peterlin⁴

From the Department of Medicine, University of California, San Francisco, California 94143, Division of Experimental Medicine, ^||HIV/AIDS Division, and ^**Department of Epidemiology and Biostatistics, San Francisco General Hospital, University of California, San Francisco, California 94143, and ^¶Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210

Human immunodeficiency virus (HIV) persists in a latent form in infected individuals treated effectively with highly active antiretroviral therapy (HAART). In part, these latent proviruses account for the rebound in viral replication observed after treatment interruption. A major therapeutic challenge is to purge this reservoir. In this study, we demonstrate that suberoylanilide hydroxamic acid (SAHA) reactivates HIV from latency in chronically infected cell lines and primary cells. Indeed, P-TEFb, a critical transcription cofactor for HIV, is released and then recruited to the viral promoter upon stimulation with SAHA. The phosphatidylinositol 3-kinase/Akt pathway is involved in the initiation of these events. Using flow cytometry-based single cell analysis of protein phosphorylation, we demonstrate that SAHA activates this pathway in several subpopulations of T cells, including memory T cells that are the major viral reservoir in peripheral blood. Importantly, SAHA activates HIV replication in peripheral blood mononuclear cells from individuals treated effectively with HAART. Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans.

---

Received for publication, October 15, 2008 , and in revised form, January 9, 2009.

^* This work was supported, in whole or in part, by National Institutes of Health Grants AI49104 and AI058708 (to B. M. P.) and R01 AI40312 and AI47062 (to J. M. M.). This work was also supported by the University of California, San Francisco, Center for AIDS Research Grants P30 AI027763, P30 MH59037, and CC99-SF-001 and the University of California, San Francisco, Clinical and Translational Research Institute Grant UL1 RR024131, a component of the National Institutes of Health Roadmap for Medical Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by a grant from the California Foundation for AIDS Research.

² Supported by the University-wide AIDS Research Program Grant F05-GI-219.

³ Recipient of National Institutes of Health Grant DPI OD00329 (Director's Pioneer Award Program, part of the National Institutes of Health Roadmap for Medical Research) and the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.

⁴ To whom correspondence should be addressed: University of California, San Francisco, 533 Parnassus Ave., Rm. U432, Box 0703, San Francisco, CA 94143. Fax: 415-502-1901; E-mail: matija.peterlin@ucsf.edu.

http://www.jbc.org/cgi/content/abstract/284/11/6782

New Type Of Vaccination Provides Instant Immunity To Two Types Of Cancer In Animal Model

ScienceDaily (Mar. 4, 2009) — The experiments, thus far performed only in mice, appear to overcome a major drawback of vaccinations – the lag time of days, or even weeks, that it normally takes for immunity to build against a pathogen. This new method of vaccination could potentially be used to provide instantaneous protection against diseases caused by viruses and bacteria, cancers, and even virulent toxins.

The team, led by Scripps Professor Carlos Barbas, III, Ph.D., tested the vaccination method – called covalent immunization – on mice with either melanoma or colon cancer.

The scientists injected these mice with chemicals specifically designed to trigger a programmable and "universal" immune reaction. They developed other chemicals, "adapter" molecules," that recognized the specific cancer cells. Once injected into the animal, the adapter molecules self-assembled with the antibodies to create covalent antibody-adapter complexes.

"The antibodies in our vaccine are designed to circulate inertly until they receive instructions from tailor-made small molecules to become active against a specific target," Barbas says. "The advantage of this method is that it opens up the possibility of having antibodies primed and ready to go in the time it takes to receive an injection or swallow a pill. This would apply whether the target is a cancer cell, flu virus, or a toxin like anthrax that soldiers or even civilian populations might have to face during a bioterrorism attack."

Only those mice that received both the vaccine and the adapter compound generated an immediate immune attack on the cancer cells that led to significant inhibition of tumor growth. This is the first time that such a covalent vaccine has been successfully designed and tested – typically, antibodies do not bind to chemicals in this covalent fashion.

The current breakthrough builds on work the Barbas laboratory has been engaged in for the past few years on chemically programmed monoclonal antibodies, a new class of therapeutics that the group invented. In this type of therapy, small, cell-targeting molecules and non-targeting catalytic monoclonal antibodies self-assemble to target pathogens. Monoclonal antibodies are produced in the laboratory from a single cloned B-cell – the immune system cell that makes antibodies – to bind to a specific substance. Three clinical trials are now under way by Pfizer to test the therapeutic effectiveness of this new type of therapy in cancer and diabetes. The antibodies in the antibody-adapter complex are monoclonal antibodies engineered to link themselves to adapter molecules.

The Search for the Ideal Vaccination

The practice of vaccination has been extraordinarily successful in controlling certain diseases, but there are drawbacks. Vaccine development can be an educated guessing game – in the case of the flu, for example, scientists must study worldwide outbreak patterns to anticipate which type of flu might strike a particular area. In addition, the most common vaccination strategies use whole proteins, viruses, or other complex immunogens – not just the specific part of the macromolecule that is recognized by the immune system – to elicit an immune response, which makes for wasted immune activity. Then there is the body's own kinetics – the time it takes to mount a disease-relevant immune response to immunogens limits the speed with which immunity can be achieved. Finally, age-related declines in the ability to mount strong immune responses to biological-based vaccines present another challenge to the effectiveness of such vaccines.

Barbas's chemical-based – rather than biological based – approach to vaccine development addresses many of these challenges.

"Our approach differs from the traditional vaccine approach in the sense that when we design an antibody-adapter compound we know exactly what that compound will react with," Barbas says. "The importance of this is best exemplified with HIV. In current vaccines, many antibodies are generated against HIV, but most are not able to target the active part of the virus."

In the near term, Barbas will apply his covalent vaccination approach to HIV, cancer, and infectious diseases for which no vaccines currently exist. A particular focus will be creating adapter molecules specific to these diseases.

"We believe that chemistry-based vaccine approaches have been underexplored and may provide opportunities to make inroads into intractable areas of vaccinology," Barbas says.

The study was funded by the Skaggs Institute for Chemical Biology and the National Institutes of Health.

---

Journal reference:

1. Mikhail Popkov et al. Instant immunity through chemically programmable vaccination and covalent self-assembly. Proceedings of the National Academy of Sciences, March 2, 2009

Adapted from materials provided by Scripps Research Institute.

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NanoViricides Anti-HIV Lead Drug Candidate Demonstrated Substantial Improvement in Survival Time in Animal Model

Results Better Than Combination Therapy in Double-Blind Animal Study

Last update: 7:00 a.m. EDT June 16, 2008

WEST HAVEN, Conn., Jun 16, 2008 (BUSINESS WIRE) -- NanoViricides, Inc. (OTC BB: NNVC.OB), (the "Company") said that its lead anti-HIV drug candidate demonstrated markedly superior survival results in the test animals when compared to those animals given the anti-HIV "combo cocktail" in a double-blind animal study. The three-drug combo "cocktail" used for comparison is one of the most frequently used triple combination therapies in humans.

The Company reported that the best nanoviricide anti-HIV drug candidate improved total hours of survival time by 99% with respect to appropriate controls. In contrast, the combo therapy improved survival hours by only 52%. Furthermore, AZT, the first drug used in humans to treat HIV/AIDS, failed to show any survival improvement, as was expected, in this lethality-based animal model study.

The Company also reported that the average body weight loss, a measure of the degree of illness in the experimental subjects, was only 11.4% after treatment with this nanoviricide drug candidate, as compared to 12.9% in those treated with the combo cocktail, and to 23% average body weight loss seen in the untreated control mice.

"We believe these are dramatic results," said Eugene Seymour, MD, MPH, CEO of the Company, adding that "if these results can be duplicated in humans, triple combo therapy with its toxic side effects may well be replaced in the near future with a much safer single HivCide-I (TM) nanoviricide therapy."

"Another advantage of the HivCide-I nanoviricide is that the treatment can be combined with other existing drug regimens for substantial added benefits," said Anil R. Diwan, PhD, President of the Company and inventor of the technology, explaining further that "strong improvements should be possible when a nanoviricide is combined with conventional regimen because nanoviricides are designed to act by a novel and completely different mechanism from existing anti-retroviral drugs."

"As for vaccines (against HIV), it was difficult to predict when they would be developed, but it could be some 10 years from the present time," remarked Dr. Anthony S. Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases, at the United Nations General Assembly High Level HIV/AIDS Meeting held on June 10
( http://www0.un.org/News/briefings/docs/2008/080610_AIDS.doc.htm ).

Several high level officials have stressed the need for development of better drugs against HIV. Jean-Francois Delfraissy, Director of France's National Agency for Research on AIDS and Viral Hepatitis, said that research "must continue to develop new therapeutic strategies," in Senegal on May 27, according to xinhuanet
( http://www.medicalnewstoday.com/articles/109257.php).

AZT is a well known anti-retroviral nucleoside reverse transcriptase inhibitor (NRTI). The combo cocktail employed as a positive control in this study consisted of AZT, 3TC (another NRTI), and Crixivan(R) (Merck, a Protease Inhibitor), administered orally. All other drugs were administered as injections. Treatment was started 24 hrs after the mice were infected with high (1200 LD50) levels of mouse-adapted HIV-I virus particles. Treatment was repeated twice more at 48 hr intervals.

The studies were performed at a Bio-Safety Level 3 Laboratory (BSL-3) facility in Boston, MA. These mouse model studies were conducted by Dr. Krishna Menon, PhD, VMD, MRCS, a world-renowned authority in preclinical and toxicological studies of innovative therapeutics.

The Company plans to report additional results from this study as they become available over the next several weeks. The Company is now designing additional studies with the objective of filing an investigational new drug application (IND) to the FDA in the future.

About NanoViricides:

NanoViricides, Inc. ( www.nanoviricides.com) is a development stage company that is creating special purpose nanomaterials for viral therapy. The Company's novel nanoviricide(TM) class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. The Company is developing drugs against a number of viral diseases including H5N1 bird flu, seasonal influenza, HIV, EKC (epidemic kerato-conjunctivitis or severe pink eye disease), hepatitis C, rabies, dengue fever, and Ebola virus, among others.

SOURCE: NanoViricides, Inc.

NanoViricides, Inc.
Amanda Schuon, 310-550-7200
info@nanoviricides.com

Source

Anti-HIV NanoViricide Drug Candidate Demonstrates Significant Therapeutic Efficacy in Animal Trials

Positive Initial Results Pave the Way for Definitive Follow-Up Studies

Last update: 7:00 a.m. EDT May 5, 2008

WEST HAVEN, Conn., May 05, 2008 (BUSINESS WIRE) -- NanoViricides, Inc. (OTC BB: NNVC.OB), said that its anti-HIV drug candidates demonstrated significant therapeutic efficacy in the recently completed preliminary animal studies. The studies were performed at a Bio-Safety Level 3 Laboratory (BSL-3) facility in Boston, MA. These mouse model studies were conducted by Dr. Krishna Menon, PhD, VMD, MRCS, a world-renowned authority in preclinical and toxicological studies of innovative therapeutics.

"Dr. Menon has indicated to us that the results of the study validate the Company's HivCide-I as a potential treatment for HIV/AIDS," said Eugene Seymour, MD, MPH, CEO of NanoViricides, adding, "Over the next several weeks, we expect to release additional study data." The Company's scientists are now designing the protocol for a follow up anti-HIV study to be performed at a major United States government research facility.

The Company also said that animal studies for its drug candidates against bird flu (H5N1) are due to be scheduled at a major United States government research facility. The company has previously reported that animal studies against Ebola would be undertaken following the success of in vitro studies. These studies are continuing.

NanoViricides, Inc. is using injectable nanoviricides for its initial HIV studies. Future plans call for the development of a long-acting anti-HIV skin patch. The Company feels that this delivery method will result in markedly improved patient compliance.

About NanoViricides: NanoViricides, Inc. ( www.nanoviricides.com) is a development stage company that is creating special purpose nanomaterials for viral therapy. The Company's novel nanoviricide(TM) class of drug candidates are designed to specifically attack enveloped virus particles and to dismantle them. The Company is developing drugs against a number of viral diseases including H5N1 bird flu, seasonal influenza, HIV, hepatitis C, rabies, dengue fever, and Ebola virus, among others.

SOURCE: NanoViricides, Inc.

NanoViricides, Inc.
Amanda Schuon, 310-550-7200
info@nanoviricides.com

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