Antiviral medication
Antiviral medications have proven useful in the prophylaxis and treatment of a many of viral diseases. Unfortunately, no antiviral medications are FDA approved specifically for the treatment of WNV.
Antivirals are a class of medications that interfere with viral replication. Viral replication may be vulnerable at one or more stages in the viral life cycle. Antivirals employ various strategies to block or delay advancement to the next stage in viral replication:
Stage |
Strategy |
Attachment |
Block viral surface proteins from binding to target cell receptors |
Fusion |
Block viral/host membrane fusion |
Uncoating |
Block disassembly of protective layer surrounding viral genome |
Transcription |
Corrupt or block the production of viral mRNA |
Protein synthesis |
Block ribosome assembly of proteins |
Maturation |
Block the cleavage and activation of viral proteins chains |
Release |
Block the attachment of viral components to the inside surface of the host cell membrane |
Several antiviral drugs have been in clinical trials and compassionate use for WNV. No treatments have shown sufficient benefit to be recommended by the CDC
- Ribavirin, used in conjunction with interferon preparations, has been shown to effectively suppress the flavivirus hepatitis C in patients. Ribavirin has also demonstrated some effectiveness against WNV in vitro. Unfortunately, ribavirin treatment involves a dose dependent risk of hemolytic anemia and possible birth defects. As yet, studies have not supported FDA approval of ribavirin as a therapy for WNV.
- "Antisense" compounds are a more focused strategy than single nucleoside analog molecules like ribavirin. Unlike ribavirin, which binds to anything it can, the "antisense" drugs in clinical trials are chains of nucleotides, tailor made to bind to specific sequences on viral RNA "sense" strands. "Sense" strands are the viral RNA used as templates to produce viral proteins; hence "antisense". Similar to ribavirin, "antisense molecules block the assembly of viral proteins.
- Interferons are potent antiviral agents produced by infected or stressed cells. Interferons released from infected cells warn neighboring cells, activating an antiviral readiness state. When viruses enter an interferon activated cell, their presence triggers production of agents that break down the mRNA of both the virus and the host cell. Protein synthesis is therefore compromised. This can result in host cell destruction but the viral infection is often cleared or inhibited.
Recently, researchers led by Dr. Michael Gale at the University of Texas Southwestern Medical Center, have found that the more pathogenic strains of WNV block host cell ability to produce interferon. They do so by blocking "the signaling activity of a protein receptor called the interferon alpha/beta receptor, or IFNAR, disrupting a cell's ability to direct the immune system to fight off the virus." ".....antiviral therapy has to embrace drugs that modulate the interferon response, and this must be coupled with early diagnosis of infection by the physician".
- Human Immune Globulin containing high titers of WNV antibodies completed clinical trials conducted by the National Institutes of Health. Omr-IgG-am is a trademarked product prepared by the Omrix Biopharmaceutical, Inc. Omr-IgG-am is prepared from the blood of WNV survivors.
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