Drugs as Molecular Tools

  • Frank J. Dutko
  • Donald E. Baright
  • Guy D. Diana
  • M. Pat Fox
  • Daniel C. Pevear
  • Mark A. McKinlay
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 312)

Abstract

Chemotherapeutic agents such as acyclovir and zidovudine have been extremely useful in treating patients with herpes simplex virus infections or AIDS, respectively. However, there is another scientific use for drugs or compounds which is to use them as molecular tools in the research laboratory in order to dissect the replication of viruses and to discover new facts about viruses. For example, alpha-amanitin, an inhibitor of the cellular DNA-dependent RNA polymerase II (Pol II), is used to define whether a particular virus RNA species is synthesized with the involvement of Pol II or solely by viral polymerases. With herpesviruses, cycloheximide, an inhibitor of protein synthesis, is used to define the “immediate early” class of viral genes. If a viral RNA is synthesized in the presence of cycloheximide, then the synthesis of that viral RNA is not dependent on the synthesis of any viral protein and that viral gene can be classified as immediate early. Arabinosyl cytosine (AraC) is an anticancer/antiherpesvirus drug which inhibits DNA synthesis in cell culture systems but allows RNA and protein synthesis to proceed. One can ask whether the replication of an RNA virus is dependent on cellular DNA synthesis by determining if virus replication is sensitive to AraC. These examples demonstrate how chemotherapeutic agents can be used as molecular tools in the research laboratory.

Keywords

Binding Affinity Antiviral Activity Molecular Tool Hydrophobic Pocket Herpes Simplex Virus Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Badger, J., Minor I., Kremer, M.J., Oliveira, M.A., Smith, T.J., Griffith, J.P., Geurin, D.M.A., Krishnaswamy, S., Luo, M. Rossmann, M.G., McKinlay, M.A., Diana, G.D., F.J. Dutko, F.J., Fancher, M., Reuckert, R.R., and Heinz, B., Structural Analysis of a Series of Antiviral Agents Complexed With Human Rhinovirus 14, Proc. Natl. Acad. Sci. USA 85:3304 (1988).CrossRefPubMedGoogle Scholar
  2. Colonno, R.J., Condra, J.H., Mitutani, S., Callahan, P.L., Davies, M.-E., and Murcko, M.A., Evidence for the Direct Involvement of the Rhinovirus Canyon in Receptor Binding, Proc. Natl. Acad. Sci. USA 85:5449 (1988).CrossRefPubMedGoogle Scholar
  3. Fox, M.P., Otto, M.J., and McKinlay, M.A., Prevention of Rhinovirus and Poliovirus Uncoating by WIN 51711, A New Antiviral Drug, Antimicrob. Ag. and Chemo. 30:110 (1986).CrossRefGoogle Scholar
  4. Fox, M.P., McKinlay, M.A., Diana, G.D., and Dutko, F.J., Binding Affinities of Structurally Related Human Rhinovirus Capsid-Binding Compounds are Related to Their Activities Against Human Rhinovirus Type 14, Antimicrob. Ag. and Chemo., 35 (6), In Press, June, 1991.Google Scholar
  5. Heinz, B.A., Reuckert, R.R., Shepard, D.A., Dutko, F.J., McKinlay, M.A., Fancher, M., Rossmann, M.G., Badger, J., and Smith, T.J., Genetic and Molecular Analyses of Spontaneous Mutants of Human Rhinovirus 14 that are Resistant to an Antiviral Compound, J. Virol. 63:2476 (1989).PubMedGoogle Scholar
  6. Kim, S., Smith, T.J., Chapman, M.S., Rossmann, M.G., Pevear, D.C., Dutko, F.J., Felock, P.J., Diana, G.D., and McKinlay, M.A., Crystal Structure of Human Rhinovirus Serotype lA (HRV1A), J. Mol. Biol.210:91 (1989).CrossRefPubMedGoogle Scholar
  7. Pevear, D.C., Fancher, M.J., Felock, P.J., Rossmann, M.G., Miller, M.S., Diana, G., Treasurywala, A.M., McKinaly, M.A., and Dutko, F.J., Conformational Change in the Floor of the Human Rhinovirus Canyon Blocks Adsorption to HeLa Cell Receptors, J. Virol. 63:2002 (1989).PubMedGoogle Scholar
  8. Smith, T.J., Kremer, M.J., Luo, M., Vriend, G., Arnold, E., Kamer, G., Rossmann, M.G., McKinlay, M.A., Diana, G.D., and Otto, M.J., The Site of Attachment in Human Rhinovirus 14 for Agents that Inhibit Uncoating, Science 233:1286 (1986).CrossRefPubMedGoogle Scholar
  9. Strikas, R.A., Anderson, L.J., and Parker, R.A., Temporal and Geographic Patterns of Isolates of Nonpolio Enterovirus in the United States, 1970–1983, J. Inf. Dis. 153:346 (1986).CrossRefGoogle Scholar
  10. Woods, M.G., Diana, G.D., Rogge, M.C., Otto, M.J., Dutko, F.J., and McKinlay, MA., In Vitro and In Vivo Activities of WIN 54954, A New Broad-Spectrum Antipicornavirus Drug, Antimicrob. Ag. and Chemo. 33:2069 (1989).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Frank J. Dutko
    • 1
  • Donald E. Baright
    • 1
  • Guy D. Diana
    • 2
  • M. Pat Fox
    • 1
  • Daniel C. Pevear
    • 1
  • Mark A. McKinlay
    • 1
  1. 1.Departments of VirologySterling Research GroupRensselaerUSA
  2. 2.Medicinal ChemistrySterling Research GroupRensselaerUSA

Personalised recommendations