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Overview
Alios is discovering and developing novel therapeutic agents based on three platform technologies including: small molecule activators of innate immunity antiviral pathways (RNase L activation), phosphate protected nucleotide prodrug chemistry, and glycoprotein-engineering of interferons (Glycoferonâ). This complementary group of platform technologies has the potential to generate a number of distinct therapeutic products to treat a variety of serious viral infections such as chronic hepatitis B and C, HIV infection, and respiratory viruses (e.g. pandemic influenza) and emerging viral diseases (e.g. SARS).
Traditional approaches to antiviral therapy have utilized agents that directly inhibit viral encoded enzymes. Although quite successful, traditional direct antiviral approaches have significant challenges. Since the direct antiviral therapeutic approaches target viral encoded proteins, these medicines have a limited spectrum of activity and are often only effective against one type of virus. The second challenge is the emergence of drug resistance. In most cases, monotherapy of any direct antiviral agent will lead to drug resistance. This is the reason that antiviral agents of different mechanisms are combined. Finally, in order to use a direct antiviral agent, a clear diagnosis of the infecting virus must be made and thus emergent viruses are often difficult to treat until direct antiviral agents can be produced. This can take years to accomplish. Alios is taking a novel approach to virology by utilizing activation of a component of the host innate immune system (RNase L) to create broad-spectrum antiviral agents. The Alios small molecule activators of innate immunity work by binding to an enzyme called RNase L. RNase L is present in most human cells and is naturally activated during viral infections following cellular stimulation by a protein hormone called interferon. Once activated, RNase L goes on to destroy viral RNA genomes and thus blocks the virus from reproducing. In the second platform program, Alios scientists have discovered a way to create improved versions of existing antiviral agents called nucleosides. Nucleosides work by mimicking cellular nucleotides (the building blocks of RNA and DNA) and inhibit RNA or DNA synthesis. A nucleoside is unphosphorylated and must rely on cellular enzymes to attach phosphate groups in order to create active nucleotide compounds. Alios scientists, working in collaboration with the world renowned nucleotide chemist Dr. Harry Lundberg, Ph.D. at the University of Turku, have synthesized phosphate protected nucleotide prodrugs, and have demonstrated that cellular enzymes can metabolize the protected prodrugs into authentic nucleotide-monophosphate analogs. |







