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. 2008 Apr 10;19:117–126. doi: 10.1016/S0065-7743(08)60688-0

Chapter 12. Antiviral Agents

James L Kelley 1
PMCID: PMC7172521  PMID: 32336813

Publisher Summary

This chapter discusses the agents with activity primarily against RNA viruses. The communicable diseases of the respiratory tract are probably the most common cause of symptomatic human infections. The viruses that are causative agents for human respiratory disease comprise the five taxonomically distinct families: orthomyxoviridae, paramyxoviridae, picornaviridae, coronaviridae, and adenoviridae. The influenza viruses, which consist of types A, B, and C, belong to the family orthomyxoviridae. Types A and B have been associated with significant increases in mortality during epidemics. The disease may be asymptomatic or cause symptoms ranging from the common cold to fatal pneumonia. Immunization against influenza has been recommended for high-risk groups and antiviral chemotherapy (amantadine) is available for the treatment and prophylaxis of all influenza A infections. There is both a great need for and interest in developing a chemotherapeutic agent for the treatment of these two viral, respiratory tract pathogens. The family picornaviridae contains the genus Rhinovirus that is composed of over a hundred distinct serotypes. Amantadine and rimantadine are specifically active against influenza A virus infections. The amantadine recipients reported a higher incidence of side effects largely attributed to the central nervous system (CNS) symptoms. This difference in side effects may be a pharmacokinetic phenomenon that results in higher plasma concentrations of amantadine. Significant progress continues to be made in the clinical use and development of agents active against DNA viruses. Acyclovir (9-(2-h droxyethoxymethyl)guanine) has been the subject of several reviews and of a syrnposium. Considerable progress has been made in evaluating the clinical promise of acyclovir; however, there remains much to be learned concerning the best use of this drug in clinical practice. Significant strides have been made in the development of clinically useful antiviral agents, especially against the DNA viruses of the herpes family. Most of these agents are directed against viral nucleic acid synthesis and require activation by a virus-induced thymidine kinase. Researchers have begun to focus on other strategies that may produce broader spectrum anti-viral agents with different mechanisms of action.

References

  • 1.Kelley J.L., Beauchamp L. Annu. Rep. Med. Chem. 1983;18:139. [Google Scholar]
  • 2.Drach J.C., Sidwell R.W. Annu. Rep. Med. Chem. 1981;16:149. [Google Scholar]
  • 3.Schinazi R.F., Prusoff W.H. Pediatr. Clin. North Am. 1983;30:77. doi: 10.1016/s0031-3955(16)34322-x. [DOI] [PubMed] [Google Scholar]
  • 4.Hermans P.E., Cockerill F.R., III Mayo Clin. Proc. 1983;58:217. [PubMed] [Google Scholar]
  • 5.Douglas R.G., Jr. Medical Clin. North Am. 1983;67:1163. doi: 10.1016/s0025-7125(16)31172-5. [DOI] [PubMed] [Google Scholar]
  • 6.Bukrinskaya A.G. Advances in Virus Research. 1982;27:141. doi: 10.1016/s0065-3527(08)60435-2. [DOI] [PubMed] [Google Scholar]
  • 7.Tyeryar F.J. J. Infect. Dis. 1983;148:588. doi: 10.1093/infdis/148.3.588. [DOI] [PubMed] [Google Scholar]
  • 8.Anderson L.J., Patriarca P.A., Hierholzer J.C., Noble G.R. Medical Clin. North Am. 1983;67:1009. doi: 10.1016/S0025-7125(16)31164-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lennette E.H. Bull. W. H.O. 1981;59:305. [PMC free article] [PubMed] [Google Scholar]
  • 10.Galasso G.J. Antiviral Res. 1981;1:73. doi: 10.1016/0166-3542(81)90035-8. [DOI] [PubMed] [Google Scholar]
  • 11.Bryson Y.J. Pediatr. Infect. Dis. 1982;1:44. doi: 10.1097/00006454-198201000-00014. [DOI] [PubMed] [Google Scholar]
  • 12.Zlydnikov D.M., Kubar O.I., Kovaleva T.P., Kamforin L.E. Rev. of Infect. Dis. 1981;3:408. doi: 10.1093/clinids/3.3.408. [DOI] [PubMed] [Google Scholar]
  • 13.Dolin R., Reichman R.C., Madore H.P., Maynard R., Linton P.N., Webber-Jones J. N. Engl. J. Med. 1982;307:580. doi: 10.1056/NEJM198209023071002. [DOI] [PubMed] [Google Scholar]
  • 14.Van Voris L.P., Betts R.F., Hayden F.G., Christmas W.A., Douglas R.G. J. Am. Med. Assoc. 1981;245:1128. doi: 10.1001/jama.245.11.1128. [DOI] [PubMed] [Google Scholar]
  • 15.Quarles J.M., Courch R.B., Cate J.R., Goswick C.B. Antiviral Res. 1981;1:149. doi: 10.1016/0166-3542(81)90003-6. [DOI] [PubMed] [Google Scholar]
  • 16.Hayden F.G., Hoffman H.E., Spyker D.A. Antimicrob. Agents Chemother. 1983;23:458. doi: 10.1128/aac.23.3.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Millet V.M., Dreisbach M., Bryson Y.J. Antimicrob. Agents Chemother. 1982;21:1. doi: 10.1128/aac.21.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Flaherty J.A., Bellur S.N. J. Clin. Psychiatry. 1981;42:344. [PubMed] [Google Scholar]
  • 19.Horadam V.W., Sharp J.G., Smilack J.D., McAnalley B.H., Garriott J.C., Stephens M.K., Prati R.C., Brater D.C. Ann. Intern. Med. 1981;94:454. doi: 10.7326/0003-4819-94-4-454. [DOI] [PubMed] [Google Scholar]
  • 20.Wu M.J., Ing T.S., Soung L.S., Daugirdas J.T., Hano J.E., Gandhi V.C. Clin. Nephrol. 1982;17:19. [PubMed] [Google Scholar]
  • 21.Bukrinskaya A.G., Vorkunova N.K., Kornilayeva G.V., Narmanbetova R.A., Vorkunova G.K. J. Gen. Virol. 1982;60:49. doi: 10.1099/0022-1317-60-1-49. [DOI] [PubMed] [Google Scholar]
  • 22.Bukrinskaya A.G., Vorkunova N.K., Pushkarskaya N.L. J. Gen. Virol. 1982;60:61. doi: 10.1099/0022-1317-60-1-61. [DOI] [PubMed] [Google Scholar]
  • 23.Koff W.C., Elm J.L., Jr., Halstead S.B. Am. J. Trop. Med. Hyg. 1981;30:184. doi: 10.4269/ajtmh.1981.30.184. [DOI] [PubMed] [Google Scholar]
  • 24.Fisher D.A. Cutis. 1982;29:467. [PubMed] [Google Scholar]
  • 25.A.W. Galbraith, Brit. J. Clinical Practice, September, 304 (1983). [PubMed]
  • 26.Chang T.W., Heel R.C. Drugs. 1981;22:111. doi: 10.2165/00003495-198122020-00002. [DOI] [PubMed] [Google Scholar]
  • 27.Knight V., McClung H.W., Wilson S.Z., Waters B.K., Quarles J.M., Cameron R.W., Greggs S.E., Zerwas J.M., Couch R.B. Lancet. 1981;2:945. doi: 10.1016/s0140-6736(81)91152-1. [DOI] [PubMed] [Google Scholar]
  • 28.McClung H.W., Knight V., Gilbert B.E., Wilson S.Z., Quarles J.M., Divine G.W. J. Am. Med. Assoc. 1983;249:2671. [PubMed] [Google Scholar]
  • 29.Hruska J.F., Morrow P.E., Suffin S.C., Douglas R.G., Jr. Antimicrob. Agents Chemother. 1982;21:125. doi: 10.1128/aac.21.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Hall C.B., Walsh E.E., Hruska J.F., Betts R.F., Hall W.J. J. Am. Med. Assoc. 1983;249:2666. [PubMed] [Google Scholar]
  • 31.Hall C.B., McBride J.T., Walsh E.E., Bell D.M., Gala C.L., Hildreth S., Ten Eyck L.G., Wall W.J. N. Engl. J. Med. 1983;308:1443. doi: 10.1056/NEJM198306163082403. [DOI] [PubMed] [Google Scholar]
  • 32.Smee D.F., Sidwell R.W., Clark S.M., Barnett B.B., Spendlove R.S. Antimicrob. Agents Chemother. 1981;20:533. doi: 10.1128/aac.20.4.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Koff W.C., Pratt R.D., Elm J.L., Jr., Venkateshan C.N., Halstead S.B. Antimicrob. Agents Chemother. 1983;24:134. doi: 10.1128/aac.24.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Koff W.C., Elm J.L., Halstead S.B. Antiviral Res. 1982;2:69. doi: 10.1016/0166-3542(82)90027-4. [DOI] [PubMed] [Google Scholar]
  • 35.Srivastava P.C., Robins R.K. J. Med. Chem. 1983;26:445. doi: 10.1021/jm00357a024. [DOI] [PubMed] [Google Scholar]
  • 36.Kirsi J.J., North J.A., McKernan P.A., Murray B.K., Canonico P.G., Huggins J.W., Srivastava P.C., Robins R.K. Antimicrob. Agents Chemother. 1983;24:353. doi: 10.1128/aac.24.3.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.De Clercq E., Montgomery J.A. Antiviral Res. 1983;3:17. doi: 10.1016/0166-3542(83)90011-6. [DOI] [PubMed] [Google Scholar]
  • 38.Phillpotts R.J., Jones R.W., DeLong D.C., Reed S.E., Wallace J., Tyrrel D.A.J. Lancet. 1981;1:1342. doi: 10.1016/s0140-6736(81)92520-4. [DOI] [PubMed] [Google Scholar]
  • 39.Phillpotts R.J., Wallace J., Tyrrell D.A.J., Tagart V.B. Antimicrob. Agents Chemother. 1983;23:671. doi: 10.1128/aac.23.5.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Hayden F.G., Gwaltney J.M., Jr. Antimicrob. Agents Chemother. 1982;21:892. doi: 10.1128/aac.21.6.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Levandowski R.A., Pachucki C.T., Rubenis M., Jackson G.G. Antimicrob. Agents Chemother. 1982;22:1004. doi: 10.1128/aac.22.6.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Herrmann E.C., Jr., Herrmann J.A., DeLong D.C. Antiviral Res. 1981;1:301. doi: 10.1016/0166-3542(82)90003-1. [DOI] [PubMed] [Google Scholar]
  • 43.C.J. Paget D.C. DeLong J. Nelson J.H. Wikel, Abstracts, 185th American Chemical Society National Meeting, Seattle, Washington, March 20–25, 1983; No. CARB 31.
  • 44.C. Paget J. Wikel T. Morwick T. Suarez D. DeLong J. Nelson J. Quay R. Bopp, Abstracts, North American Medicinal Chemistry Symposium, University of Toronto, Toronto, Canada, June 20–24, 1982; Poster 94.
  • 45.Eggers H.J. Handb. Exp. Pharmacol. 1982;61:377. [Google Scholar]
  • 46.Herrmann E.C., Jr., Herrmann J.A., DeLong D.C. Antiviral Res. 1982;2:339. doi: 10.1016/0166-3542(82)90003-1. [DOI] [PubMed] [Google Scholar]
  • 47.Dubovi E.J., Geratz J.D., Shaver S.R., Tidwell R.R. Antimicrob. Agents Chemother. 1981;19:649. doi: 10.1128/aac.19.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Tidwell R.R., Geratz J.D., Dubovi E.J. J. Med. Chem. 1983;26:294. doi: 10.1021/jm00356a036. [DOI] [PubMed] [Google Scholar]
  • 49.Bauer D.J., Selway J.W.T., Batchelor J.F., Tisdale M., Caldwell I.C., Young D.A.B. Nature. 1981;292:369. doi: 10.1038/292369a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Tisdale M., Selway J.W.T. J. Gen. Virol. 1983;64:795. doi: 10.1099/0022-1317-64-4-795. [DOI] [PubMed] [Google Scholar]
  • 51.Phillpotts R.J., Wallace J., Tyrrell D.A.J., Freestone D.S., Shepherd W.M. Arch. Virol. 1983;75:115. doi: 10.1007/BF01314131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Drugs of the Future. 1982;7:542. [Google Scholar]
  • 53.Ishitsuka H., Ohsawa C., Ohiwa T., Umeda I., Suhara Y. Antimicrob. Agents Chemother. 1982;22:611. doi: 10.1128/aac.22.4.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Güttner J., Veckenstedt A., Heinecke H., Pusztai R. Acta Virol. 1982;26:148. [PubMed] [Google Scholar]
  • 55.Veckenstedt A., Pusztai R. Antiviral Res. 1981;1:249. doi: 10.1016/0166-3542(81)90015-2. [DOI] [PubMed] [Google Scholar]
  • 56.Ishitsuka H., Ninomiya Y.T., Ohsawa C., Fujiu M., Suhara Y. Antimicrob. Agents Chemother. 1982;22:617. doi: 10.1128/aac.22.4.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Scrip: World Pharmaceutical News, No. 689, p. 13 (1982).
  • 58.Powers R.D., Gwaltney J.M., Jr., Hayden F.G. Antimicrob. Agents Chemother. 1982;22:639. doi: 10.1128/aac.22.4.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Torney H.L., Dulworth J.K., Steward D.L. Antimicrob. Agents Chemother. 1982;22:635. doi: 10.1128/aac.22.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Ohnishi H., Yamaguchi K., Shimada S., Himuro S., Suzuki Y. Antimicrob. Agents Chemother. 1982;22:250. doi: 10.1128/aac.22.2.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.M.A. McKinlay C.J. Brisson J.V. Miralles G.D. Diana in “Program and Abstracts, 23rd ICAAC”, American Society of Microbiology, Las Vegas, Nevada, 1983, Abstract 160.
  • 62.J.M. Gwaltney, Jr. and F.G. Hayden in “Program and Abstracts, 23rd ICAAC”, American Society for Microbiology, Las Vegas, Nevada, 1983, Abstract 931.
  • 63.Barry D., Blum R. In: Shand D.G., Turner P., editors. Vol. 3. Churchill Livingstone Inc.; New York: 1983. p. 57. (“Recent Advances in Clinical Pharmacology”). [Google Scholar]
  • 64.Bean B. Postgrad. Med. 1983;73(3):297. doi: 10.1080/00325481.1983.11697814. [DOI] [PubMed] [Google Scholar]
  • 65.Richards D.M., Carmine A.A., Brogden R.N., Heel R.C., Speight T.M., Avery G.S. Drugs. 1983;26:378. doi: 10.2165/00003495-198326050-00002. [DOI] [PubMed] [Google Scholar]
  • 66.Laskin O.L. Clin. Pharmacokinet. 1983;8:187. doi: 10.2165/00003088-198308030-00001. [DOI] [PubMed] [Google Scholar]
  • 67.Rudd C.C. Drug. Ther. Hosp. 1983;8(9):41. [Google Scholar]
  • 68.Rogers H.J., Fowle A.S.E. J. Clin. Hosp. Pharm. 1983;8:89. doi: 10.1111/j.1365-2710.1983.tb01038.x. [DOI] [PubMed] [Google Scholar]
  • 69.J. Antimicrob. Chemother. 1983;12(Suppl. B) [Google Scholar]
  • 70.Bryson Y.J., Dillon M., Lovett M., Acuna G., Taylor S., Cherry J.D., Johnson B.L., Wiesmeier E., Creagh-Kirk T., Keeney R. N. Engl. J. Med. 1983;308:916. doi: 10.1056/NEJM198304213081602. [DOI] [PubMed] [Google Scholar]
  • 71.Reichman R.C., Badger G.J., Mertz G.J., Corey L., Richman D., Oxman M., Connor J., Bryson Y., Tyrrell D., Partnoy J. Clin. Res. 1983;31:373A. [Google Scholar]
  • 72.Gluckman E., Lotsberg J., Devergie A., Zhao X.M., Melo R., Gomez-Morales M., Nebout T., Mazeron M.C., Perol Y. Lancet. 1983;2:706. doi: 10.1016/s0140-6736(83)92248-1. [DOI] [PubMed] [Google Scholar]
  • 73.Straus S., Seidlin M., Takiff H., Bachrach S., DiGiovanna J., Western K., Creagh-Kirk T., Lininger L., Alling D. Clin. Res. 1983;31:543A. [PubMed] [Google Scholar]
  • 74.Fiddian A.P., Yeo J.M., Stubbings R., Dean D. Br. Med. J. 1983;286:1699. doi: 10.1136/bmj.286.6379.1699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Brigden D., Keeney R.E., King D.H. J. Antimicrob. Chemother. 1983;12(Suppl. B):195. doi: 10.1093/jac/12.suppl_b.195. [DOI] [PubMed] [Google Scholar]
  • 76.Colla L., De Clercq E., Busson R., Vanderhaeghe H. J. Med. Chem. 1983;26:602. doi: 10.1021/jm00358a029. [DOI] [PubMed] [Google Scholar]
  • 77.Spector T., Jones T.E., Beacham L.M., III Biochem. Pharmac. 1983;32:2505. doi: 10.1016/0006-2952(83)90010-2. [DOI] [PubMed] [Google Scholar]
  • 78.Krasny H.C., Liao S.H.T., Good S.S. Clin. Pharmac. Ther. 1983;33:256. [Google Scholar]
  • 79.Fraser-Smith E.B., Smee D.F., Matthews T.R. Antimicrob. Agents Chemother. 1983;24:883. doi: 10.1128/aac.24.6.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Field A.K., Davies M.E., DeWitt C., Perry H.C., Liou R., Germershausen J., Karkas J.D., Ashton W.T., Johnston D.B.R., Tolman R.L. Proc. Natl. Acad. Sci. USA. 1983;80:4139. doi: 10.1073/pnas.80.13.4139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Mar E.-C., Cheng Y.-C., Huang E.-S. Antimicrob. Agents Chemother. 1983;24:518. doi: 10.1128/aac.24.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Rollinson E.A., White G. Antimicrob. Agents Chemother. 1983;24:221. doi: 10.1128/aac.24.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Scrip: World Pharmaceutical News. 1983:14. No. 834. [Google Scholar]
  • 84.Young C.W., Schneider R., Leyland-Jones B., Armstrong D., Tan C.T.C., Lopez C., Watanabe K.A., Fox J.J., Philips F.S. Cancer Res. 1983;43:5006. [PubMed] [Google Scholar]
  • 85.Philips F.S., Feinberg A., Chou T.-C., Vidal P.M., Su T.-L., Watanabe K.A., Fox J.J. Cancer Res. 1983;43:3619. [PubMed] [Google Scholar]
  • 86.Watanabe K.A., Su T.-L., Klein R.S., Chu C.K., Matsuda A., Chun M.W., Lopez C., Fox J.J. J. Med. Chem. 1983;26:152. doi: 10.1021/jm00356a007. [DOI] [PubMed] [Google Scholar]
  • 87.De Clercq E. Pure and Appl. Chem. 1983;55:623. [Google Scholar]
  • 88.Shannon W.M., Arnett G., Baker D.C., Kumar S.D., Higuchi W.I. Antimicrob. Agents Chemother. 1983;24:706. doi: 10.1128/aac.24.5.706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Vilde J.L., Bricaire F., Huchon A., Brun-Vezinet F. J. Med. Virology. 1983;12:149. doi: 10.1002/jmv.1890120209. [DOI] [PubMed] [Google Scholar]
  • 90.Shannon W.M., Westbrook L., Arnett G., Daluge S., Lee H., Vince R. Antimicrob. Agents Chemother. 1983;24:538. doi: 10.1128/aac.24.4.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Oberg B. Pharmac. Ther. 1983;19:387. doi: 10.1016/0163-7258(82)90074-2. [DOI] [PubMed] [Google Scholar]
  • 92.Norén J.O., Helgstrand E., Johansson N.G., Misiorny A., Stening G. J. Med. Chem. 1983;26:264. doi: 10.1021/jm00356a028. [DOI] [PubMed] [Google Scholar]
  • 93.Tyms A.S., Williams J.D. Nature. 1982;297:690. doi: 10.1038/297690a0. [DOI] [PubMed] [Google Scholar]
  • 94.Goswami B.B., Sharma O.K., Borek E. Recent Results in Cancer Research. 1983;84:275. doi: 10.1007/978-3-642-81947-6_21. [DOI] [PubMed] [Google Scholar]
  • 95.De Clercq E. Nucl. Acid Res., Series No. 1982;11:203. [PubMed] [Google Scholar]
  • 96.Torrence P.F., Lesiak K., Imai J., Johnston M.I., Sawai H. In: “Nucleosides, Nucleotides and Their Biological Applications”. Rideout J.L., Henry D.W., Beacham L.M. III, editors. Academic Press; New York: 1983. p. 67. [Google Scholar]
  • 97.Suhadolnik R.J., Devash Y., Doetsch P., Henderson E.E., Wu J.M., Pfleiderer W., Charubala R. In: “Nucleosides, Nucleotides and Their Biological Applications”. Rideout J.L., Henry D.W., Beacham L.M. III, editors. Academic Press; New York: 1983. p. 147. [Google Scholar]
  • 98.Lacal J.-C., Carrasco L. Antimicrob. Agents Chemother. 1983;24:273. doi: 10.1128/aac.24.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 99.Fiume L., Busi C., Mattioli A. FEBS Lett. 1983;153:6. doi: 10.1016/0014-5793(83)80108-2. [DOI] [PubMed] [Google Scholar]
  • 100.Miller D.K., Lenard J. Proc. Natl. Acad. Sci. USA. 1981;78:3605. doi: 10.1073/pnas.78.6.3605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 101.Lenard J., Miller D.K. Cell. 1982;28:5. doi: 10.1016/0092-8674(82)90368-3. [DOI] [PubMed] [Google Scholar]
  • 102.Helenius A., Marsh M., White J. J. Gen. Virol. 1982;58:47. doi: 10.1099/0022-1317-58-1-47. [DOI] [PubMed] [Google Scholar]
  • 103.Shibata M., Aoki H., Tsurumi T., Sugiura Y., Nishiyama Y., Suzuki S., Maeno K. J. Gen. Virol. 1983;64:1149. doi: 10.1099/0022-1317-64-5-1149. [DOI] [PubMed] [Google Scholar]

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