Abstract
Retrospectively, the development of antiviral agents can be divided into three phases. Drugs that were originally employed as antitumour agents were examined in the early stages for inhibition of viral replication; these included compounds such as iodine deoxyuridine and cytosine arabinoside. The former was introduced in 1962 by Herbert E. Kaufman as one of the first antiviral drugs for the local treatment of keratoconjunctivitis, which is induced by herpes simplex virus. With increased knowledge of the molecular biology of the cell and that of viruses, the predominantly empirical strategies were superseded by approaches designed to improve poorly selective agents by chemical modifications. The results of that “targeted empiricism” were drugs such as adenosine arabinoside, bromovinyl deoxyuridine and acycloguanosine. Adenosine arabinoside was the first chemotherapeutic drug that showed a healing effect on herpes simplex virus induced encephalitis and herpes infection of neonates (herpes neonatorum) by systemic, i.e. intravenous, administration. The drug acycloguanosine, which was subsequently developed by Gertrude Elion in 1977, was a breakthrough in the treatment of herpesvirus infections (Sect. 19.5). The currently established methods for sequencing viral genetic information, structural analysis of viral enzymes and recent new insights in molecular genetics allow the specific investigation of the targets of antiviral agents, including the development of so-called designer drugs. The acquired knowledge and the new insights into the pathogenesis of viral infections constitute the basis for the development of targeted, optimally configured inhibitory antimetabolites, and thus for the design of virostatic drugs. Although a series of new antiviral compounds has been developed in recent years, not least under the pressure to find ways for AIDS therapy, there are only a few effective chemotherapeutic agents today (Table 9.1), in comparison with the large number of antibiotics available to treat bacterial infectious diseases. The production of new antiviral drugs is certainly limited by the strictly intracellular replication cycle of the virus, which complicates the selection of specific targets without generating cell damage. Besides the direct inhibition of the viral replication cycle, attempts have also been undertaken to influence therapeutically the inflammation processes triggered by viral infections, by combining chemotherapeutic drugs with cytokines, as it became clear that the pathogenesis of most viral diseases is linked to viral and immunological processes (Chap. 8).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Further Reading
Blair E, Darby G, Gough G, Littler E, Rowlands D, Tinsdale M (1998) Antiviral therapy. BIOS, Oxford
Cameron CE, Castro C (2001) The mechanism of action of ribavirin: lethal mutagenesis of RNA virus genomes mediated by the viral RNA-dependent RNA polymerase. Curr Opin Infect Dis 6:757–764
Cantin EM, Woolf TM (1993) Antisense oligonucleotides as antiviral agents: prospects and problems. Trends Microbiol 1:270–275
Cohen J (1993) A new goal: preventing disease not infection. Science 262:1820–1821
Darby GK (1996) Only 35 years of antiviral nucleoside analogues! In: Hunter PA, Darby GK, Russell NJ (eds) Fifty years of antimicrobials: past perspectives and future trends. Cambridge University Press, Cambridge
Field AK, Biron KK (1994) “The end of innocence” revisited: resistance of herpesvirus to antiviral drugs. Clin Microbiol Rev 7:1–13
Galasso GJ, Boucher CAB, Cooper DA (2002) Practical guidelines in antiviral therapy. Elsevier, Amsterdam
Haasnoot J, Westerhout EM, Berkhout B (2007) RNA interference against viruses: strike and counterstrike. Nat Biotechnol 25:1435–1443
Koup RA, Brewster F, Grab P, Sullivan JL (1993) Nevirapine synergistically inhibits HIV1 replication in combination with zidovudine, interferon or CD4 immunoadhesin. AIDS 7:1181–1184
Kuritzkes DR (2009) HIV-1 entry inhibitors: an overview. Curr Opin HIV AIDS 4:82–87
Larder BA (1994) Interactions between drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J Gen Virol 75:951–957
Leemans WF, Ter Borg MJ, de Man RA (2007) Review article: success and failure of nucleoside and nucleotide analogues in chronic hepatitis B. Aliment Pharmacol Ther 26(suppl 2):171–182
Loomba R, Liang TJ (2007) Treatment of chronic hepatitis B. Antivir Ther 12(suppl 3):H33–H41
Marsden HS (1992) Antiviral therapies. Semin Virol 3:1–75
Meier V, Ramadori G (2009) Hepatitis C virus virology and new treatment targets. Expert Rev Anti Infect Ther 7:329–350
Pan Q, Tilanus HW, Janssen HL, van der Laan LJ (2009) Prospects of RNAi and microRNA-based therapies for hepatitis C. Expert Opin Biol Ther 9:713–724
Ruf BR, Szucs T (2009) Reducing the burden of influenza-associated complications with antiviral therapy. Infection 39:186–196
Steininger C (2007) Novel therapies for cytomegalovirus disease. Recent Pat Antiinfect Drug Discov 2:53–72
Stellbrink HJ (2009) Novel compounds for the treatment of HIV type1 infection. Antivir Chem Chemother 19:189–200
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Modrow, S., Falke, D., Truyen, U., Schätzl, H. (2013). Chemotherapy. In: Molecular Virology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-20718-1_9
Download citation
DOI: https://doi.org/10.1007/978-3-642-20718-1_9
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-20717-4
Online ISBN: 978-3-642-20718-1
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences