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Re: changes_iv post# 103249

Monday, 11/03/2014 12:51:24 PM

Monday, November 03, 2014 12:51:24 PM

Post# of 146240
We've been down this road before, 2010...

NanoViricides, Inc. (OTC BB: NNVC.OB) (the "Company") reports that the results of the evaluation of several of its nanoviricidesR anti-Ebola agents were presented July 17th at the Annual Meeting of the American Society for Virology, July 17-21, at Montana State University, Bozeman, MT. Dr. Corinne Scully delivered the presentation, which was entitled "Polymeric Micelle Nanomaterials as Antiviral Compounds For Ebola Virus Infection."

The studies were performed in the laboratory of Dr. Gene Olinger at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD.

In cell culture screening assays, the nanoviricidesR were evaluated for cytotoxicity and for inhibition of Ebola virus infection. Several of the nanoviricides demonstrated a dose-dependent inhibition of Ebola virus infectivity with no toxicity of uninfected cells at concentrations that were effective against the virus.

A subset of the nanoviricides that were effective in cell culture was selected for testing in vivo in a mouse model of Ebola infection. The compounds were well tolerated by the animals and showed some efficacy against the mouse-adapted Ebola virus. Efficacy of nanoviricides treatment against Ebola virus was demonstrated by an increase in lifespan in this uniformly 100% lethal animal model.

The Company developed a library of chemical ligands that were expected to bind to the Ebola virus envelope proteins. The results reported at this meeting will help guide the synthesis of next generation anti-Ebola nanoviricides in a lead optimization synthetic program. Optimized nanoviricides will also be evaluated against other similar Hemorrhagic Fever Viruses, e.g. Marburg virus.

Based on the current results and previous success with another hemorrhagic fever virus (viz. Dengue), the Company believes that it can develop a single nanoviricide drug that is highly effective against both Ebola and Marburg filoviruses. Developing a single drug against the various Ebola and Marburg viruses has been a major challenge for researchers in the field. Currently there are no approved vaccines or therapeutics for the prevention or treatment of Ebola and Marburg viruses.

Ebola/Marburg viruses are a major concern both as potential global health threats and as potential threat agents for Biosecurity and Biodefense, and are identified as Category A agents. Ebola outbreaks have resulted in fatality rates as high as 80% in humans ~ BusinessWire


(http://www.who.int/mediacentre/factsheets/fs103/en/index.html).
Quote: Marburg haemorrhagic fever

Key facts:

-The Marburg virus causes severe viral haemorrhagic fever in humans.
-Case fatality rates in Marburg haemorrhagic fever outbreaks have ranged from 24% to 88%.
-Rousettus aegypti, fruit bats of the Pteropodidae family, are considered to be natural hosts of Marburg virus. The Marburg virus is transmitted to people from fruit bats and spreads among humans through human-to-human transmission.
-No specific antiviral treatment or vaccine is available.

[Marburg and Ebola virus] Entry

Niemann-Pick C1 (NPC1) appears to be essential for Ebola and Marburg virus infection. Two independent studies reported in the same issue of Nature (journal) showed that Ebola virus cell entry and replication requires the cholesterol transporter protein NPC1.[43][44] When cells from patients lacking NPC1 were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the virus, further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Ebola's cousin in the filovirus group, Marburg virus, showing that it too needs NPC1 to enter cells.[43][44] Furthermore, NPC1 was shown to be critical to filovirus entry because it mediates infection by binding directly to the viral envelope glycoprotein.[44] A later study confirmed the findings that NPC1 is a critical filovirus receptor that mediates infection by binding directly to the viral envelope glycoprotein and that the second lysosomal domain of NPC1 mediates this binding.[45]

In one of the original studies, a small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.[44][46] In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse adapted Ebola virus.[43] Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola anti-viral drug.


http://en.wikipedia.org/wiki/Marburg_virus

Fast forward, 2014...

In other news, NanoViricides reported that the synthesis of its anti-Ebola second generation drug candidates has started. We anticipate being able to evaluate these against Ebola virus with certain of our previous collaborators. The contracts to enable such evaluation are currently in progress. The Company's nanomedicine technology enables development of drugs that directly attack the virus, in a manner that a virus may not be able to overcome despite mutational changes. This is very important for the current epidemic-causing Ebola virus strain, which has been shown to be mutating rapidly.

NanoViricides has developed additional novel drug candidates against Ebola using its nanoviricide drug process. A nanoviricide drug consists of the combination of a virus-binding ligand that mimics the native receptor on the host cell and a backbone polymer that makes the drug look like the host cell surface to the virus.

"We believe the new anti-Ebola ligands should make the new drug candidates substantially superior to our older ones, based on the molecular modeling studies we have conducted using the structural information of interaction of Ebola virus glycoprotein with its cellular receptor Niemann-Pick C1 (NPC) protein," Anil Diwan, the president of NanoViricides, said. "We believe th aat Ebola virus will not be able to avoid our drug candidates in spite of mutations, because we are mimicking NPC1, the receptor to which the virus must bind in order to infect the host cell. Of course, we must await results from actual cell culture and animal testing to further develop these candidates."


Second generation EbolaCide has new ligands, NPC1, and we anticipate superior to those of first generation EbolaCide...

WEST HAVEN, Conn.--(BUSINESS WIRE)--NanoViricides, Inc. (NYSE MKT:NNVC) (the “Company”), a nanomedicine company developing anti-viral drugs, announced today that it has executed a CRADA (Collaborative Research and Development Agreement for Material Transfer) with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Certain novel anti-Ebola nanomedicine drug candidates recently developed by the Company will be evaluated by USAMRIID scientists in their BSL-4 facilities for activity against the deadly Ebola virus under this agreement.


http://www.biospace.com/News/nanoviricides-inc-signs-crada-for-material/351709/source=MoreNews

Just a few days ahead and our BSL-4 partner/collaborator will be testing efficacy of our second generation EbolaCides candidates. Confidence is high as we've been down this road before but, this time our nanoviricides are loaded with superior ligands for Ebola and Marburg viruses!
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