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Wednesday, 08/14/2013 6:22:10 PM

Wednesday, August 14, 2013 6:22:10 PM

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Excerpt from 2009 Jain Report: Structure and function of nanoviricides

source: http://allallan.blogspot.com/2009/04/nnvc-why-so-special.html

NanoViricides are polymeric micelles, which bind to multiple virus-surface-receptors as antiviral agents.They are different from any of the other micellar nanotechnologies as there are no metal particles attached and the micelles can penetrate the virus and bind to multiple sites for effective destruction of the virus.

Mechanism of action of NanoViricides

For a virus to infect a cell, it needs to bind to more than one site. For example, binding of HIV only to CD4 on T cells is insufficient to cause sustained disease; it needs HIV binding to at least two and possibly three different sites on the T cell and that too, at multiple points. For an antiviral to be effective, it should match the strategy to bind to more than one site on the virus. Ideally it should block all of these to prevent virus from infecting the cell and multiplying. Most of the current antiviral drugs have a single mechanism of action and block a single receptor. Drug combinations from different categories are required to increase the number of receptors blocked. Still this is not fully effective.

In contrast to other approaches, a NanoViricide™ micelle can recognize and bind to more than one type of binding site on the virus. The NanoViricide™ system enables design of a drug that binds to more than one type of site - currently as many as three different sites, on the virus - for a highly effective attack. NanoViricides Inc terms this as "multi-specific targeting".

A NanoViricide™ drug goes much further than just blocking all of the binding sites of the virus. The base material of a NanoViricide™ is a specially designed polymeric micelle material. It has the ability to disassemble an HIV particle by itself. Thus, after coating the virus particle, the NanoViricide™ loosens the virus particle, and weakens it. Some virus particles will even fall apart (uncoat). This provides a further therapeutic benefit. NanoViricides plans to enhance the viral disassembly capabilities of the NanoViricides™ by attaching specially designed "molecular chisels" to the NanoViricide™. Once the NanoViricide™ micelles coat the virus particle, the attached "molecular chisels" will go to work. They literally insert themselves into the virus coat at specific vulnerable points and pry apart the coat proteins so that the virus particle falls apart readily. The mechanism of action of NanoViricide is depicted schematically in Figure 4-1.

This description is a simplification. There is no fully adequate explanation of the observed efficacy because the mechanisms of action of nanomaterials as drugs and particularly, NanoViricides in vivo, are multiple and somewhat complex. Targets for this approach include influenzas, HIV, HCV, rabies and other viruses.

Advantages of NanoViricides

NanoViricides have been compared to current approaches to viral diseases, which are seldom curative and some of the advantages include the following:

§ Specific targeting of the virus with no metabolic adverse effects on the host.
§ The biological efficacy of NanoViricides drugs may be several orders of magnitude better than that of of usual chemical drugs. This in itself may limit the potential for mutant generation.
§ There are also other key aspects of the design of NanoViricides that are expected to lead to minimizing mutant generation.
§ Nanoviricides are safe because of their unique design and the fact that they are designed to be biodegradable within the body.
§ The new technology enables rapid drug development against an emerging virus, which would be important for global bio-security against natural as well as man-made (bio-terrorism) situations. It is possible to develop a research drug against a novel life-threatening viral disease within 3-6 weeks after the infection is found, i.e. as soon as an antibody from any animal source is available.
§ It is possible to make a single NanoViricide drug that responds to a large number of viral threats by using targeting ligands against the desired set of viruses in the construction of the drug.It is possible to “tune” the specificity and range (spectrum) of a NanoViricide drug within a virus type, subtype, or strain, by appropriate choices of the targeting ligand(s).
§ The safety of NanoViricide drugs is proven now as they specifically attack the virus and not the host.
§ A variety of formulations, release profiles and routes of administration are possible.
§ Low cost of drug development, manufacture, distribution.

NanoViricide drug candidates are currently in preclinical studies. Clinical trials are planned. Initially injectable products are considered to be most effective but alternative routes of administrations such as nasal sprays and bronchial aerosols can also be developed. Various Nanoviricide products will be described further along with relevant viral diseases.

Advantages of Nanoviricides over vaccines are

§ Nanoviricides work where vaccines fail and are effective even when the immune system is impaired such as in AIDS.
§ Nanoviricides work where effective vaccines are unavailable
§ Sufficient short term protection for an individual outbreak cluster-
§ Treatment can be started after infection
§ No need to vaccinate whole world population for control of a viral epidemic

Advantages of Nanoviricides over immunoglobulin therapies are

§ Fully chemical, room-temperature stable NanoViricides can be made against many diseases.
§ Nanoviricides based on antibody fragment conjugates do not require humanized antibodies. Antibodies from virtually any source can be used for developing NanoViricides, thus significantly reducing time and cost of development.

Immunoglobulin therapies require the patient's immune system (complement system) to function well, which is often not the case in advanced disease states. NanoViricides function completely independently of the human immune system while accomplishing the same goal of reduction in viremia.z
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