Antiviral therapy has been slow to progress because:
1. Most virus infections are not life threatening
2. Since viruses replicate in cells, targeting drugs that interfere with virus replication but do not harm the cell has been difficult.
To create drugs that are specifically anti-viral, steps in the virus replication cycle are targeted:
Examples of currently successful and promising strategies:
Attachment and uncoating:
The anti-rhinovirus drug currently be tested consists of a bio-engineered soluble fragment of the ICAM-1 receptor used by most of the rhinovirus serotypes.
Rimantidine and amantidine inhibit influenza A replication by binding to the M2 ion channel in the virion. This inhibits dissociation of M1 from the nucleoprotein complexes and prevents translocation to the nucleus.
Transcription/reverse transcription:
Nucleotide analogs: When incorporated into nucleic acid, they cause chain termination. The ones that are effective have a higher affinity for viral rather than cell polymerases.
Examples: Acyclovir, gancyclovir, ribavirin, AZT, ddC.
Non-nucleoside inhibitors: These drugs bind noncompetitively to viral enzymes.
Examples: Trisodium phosphonoformate (Foscarnet), nevirapine, delaviridine
Post-translational processing:
Protease inhibitors: These drugs bind competitively to viral proteases inhibiting processing.
Examples: Saquinavir, Ritonavir
Translation/Genome Synthesis:
Antisense nucleotides: Hybridize to target complementary sequences and inhibit replication and translation
Ribozymes: Recognize target sequences in RNAs and catalyze cleavage, preventing translation and replication.
Virion assembly:
Amantidine and Rimantidine secondarily inhibit influenza A virus replication
by interacting with the M2 protein, an ion channel, and disrupting the
pH balance in the ER causes improper assembly of the HA protein..
AIDS has stimulated a revolution in development of antiviral drugs. There are currently 11 AIDS drugs in use, more than twice the number of drugs previously developed against all viruses! A major problem encountered in AIDS antiviral treatment has been the generation of drug-resistant mutants. The strategy used to overcome this has been double- and triple-drug therapy.