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Posted: June 1, 2010
NanoViricides Reports that Significant Efficacy was Achieved in Initial Studies on Dengue Virus
(Nanowerk News) NanoViricides, Inc. reports that its anti-Dengue drug candidates demonstrated significant efficacy in the recently completed preliminary cell culture studies. The studies were performed in the laboratory of Dr. Eva Harris, Professor of Infectious Diseases at the University of California, Berkeley (UC Berkeley).
Several of the anti-Dengue nanoviricides® demonstrated a dose-dependent inhibition of Dengue virus infectivity in two distinctly different cell culture models of dengue virus infection. These studies employed the serotype dengue virus 2. The Company believes that these nanoviricide drug candidates mimic a common natural host cell receptor by which the four different dengue virus serotypes bind to the body’s host cells, thus causing disease. The virus is “fooled” into thinking it has attached to its target cell and instead enters a nanoviricide nanomicelle, it is believed. A nanoviricide would thus stop the spread of the viral infection to new uninfected cells.
The Company believes that a broad-spectrum nanoviricide that is highly effective against all four dengue serotypes is now feasible, based on the current data. Such a drug would circumvent the problems caused by a phenomenon called “Antibody-Dependent-Enhancement” or “ADE”.
Dr. Eva Harris is a leading researcher in the field of dengue viruses. Her group has developed a unique animal model for dengue virus infection and disease that effectively emulates the phenomenon seen in humans, called “Antibody-Dependent Enhancement (ADE)” which is thought to lead to the increased incidence of the more severe disease, dengue hemorrhagic fever and dengue shock syndrome. Selected anti-dengue nanoviricides will be tested in preliminary animal studies using this model.
The Company developed a library of chemical ligands that are expected to bind to the dengue virus envelope proteins of several different subtypes of dengue viruses. These ligands were developed using the results of sophisticated, well established, molecular modeling software. A number of candidate nanoviricides that are capable of attacking the dengue virus were created using these ligands. A “nanoviricide” is a chemical substance made by covalently attaching a number of copies of a virus-binding ligand to a base polymeric micelle, that the Company calls TheraCour®. It is believed that when a nanoviricide binds to a virus particle, the interaction would extend to the binding of a large number of ligands to the virus surface, and the flexible nanomicelle would then engulf the virus, rendering it incapable of infecting a cell.
Dengue virus is a member of the Flaviviridae family of viruses, some of which are often spread by ticks and mosquitoes. Other important viruses in this family include Yellow Fever virus, West Nile virus and Hepatitis C virus. The market for novel treatments for Hepatitis C is estimated to be in the billions of dollars in the US alone.
When a person is exposed to dengue for the first time, the disease usually is not severe. When the same person is later infected by a different dengue serotype, the body produces antibodies against the previous dengue serotype. The new dengue virus uses these antibodies to infect more cells, thus leading to severe dengue disease. Such a secondary infection may lead to dengue hemorrhagic fever or dengue shock syndrome with high fatality rates. The ADE phenomenon has made development of vaccines and antibody therapeutics against Dengue a tremendous challenge. A vaccine works by creating antibodies against the included serotypes.
Currently there are no approved vaccines for the prevention of dengue, nor drugs for treatment of dengue virus infection. The worldwide market size for an effective anti-dengue treatment may be as large as that for Hepatitis C virus treatment, reaching billions of dollars, based on current population exposure data. Dengue, dengue hemorrhagic fever and dengue shock syndrome are emerging as serious global health problems. Dengue is endemic throughout much of the world and now threatens over 3 billion people world-wide or 40% of the world’s population. Because of its world-wide distribution, dengue is considered an emerging threat in the United States. Dengue is officially considered a “neglected tropical disease” by the World Health Organization. About 50-100 million people are infected by dengue virus every year. Recently, the government of Cali, Columbia declared a dengue emergency because of the number of dengue infections and deaths. Globalization and climate change along with changes in the ecology of the virus-carrying mosquito are accelerating the spread of the virus. Without proper treatment, DHF fatality rates can exceed 20%. (Source: WHO Dengue and dengue hemorrhagic fever Fact Sheet No. 117, March 2009; http://www.who.int/mediacentre/factsheets/fs117/en/).
About Dr. Eva Harris’ Laboratory at the University of California, Berkeley
The Harris Laboratory in the Division of Infectious Diseases in the School of Public Health at the University of California, Berkeley (www.Berkeley.edu) has developed a multidisciplinary approach to study the molecular virology, pathogenesis, and epidemiology of dengue, the most prevalent mosquito-borne viral disease in humans. Their work addresses viral and host factors that modulate disease severity. One major research focus has been the development of a mouse model to study viral tropism and pathogenesis, investigate the immune response to dengue virus infection, and evaluate candidate anti-viral therapeutics. Dr. Harris’ field work focuses on laboratory-based and epidemiological studies of dengue in endemic Latin American countries, particularly in Nicaragua, where ongoing projects include clinical and biological studies of severe dengue, a pediatric cohort study of dengue and influenza transmission in Managua, and a project on evidence-based, community-derived interventions for prevention of dengue via control of its mosquito vector.
NanoViricides, Inc. (www.nanoviricides.com) is a development stage company that is creating special purpose nanomaterials for viral therapy. The Company's novel nanoviricide™ 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 H1N1 swine flu, H5N1 bird flu, seasonal Influenza, HIV, oral and genital Herpes, viral diseases of the eye including EKC and herpes keratitis, Hepatitis C, Rabies, Dengue fever, and Ebola virus, among others.