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Chemical Compound Review

Picovir     3-[3,5-dimethyl-4-[3-(3- methyl-1,2-oxazol...

Synonyms: Pleconaril, CHEMBL29609, SureCN49383, AG-J-93292, Win-63843, ...
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Disease relevance of Picovir

  • Other potentially useful treatments, such as pleconaril for enteroviral meningoencephalitis are under clinical evaluation [1].
  • When crystals of human rhinovirus 16 (HRV16) and HRV14 are incubated with pleconaril, drug occupancy in the binding pocket is lower than when pleconaril is introduced during assembly prior to crystallization [2].
  • Located within VP1 is a hydrophobic pocket into which small-molecule antiviral compounds such as pleconaril bind and inhibit functions associated with the virus capsid [3].
  • These observations are consistent with virus yield inhibition studies and radiolabeled drug binding studies showing that the antiviral effect of pleconaril against HRV16 is greater on the infectivity of progeny virions than the parent input viruses [2].
  • Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection [4].

High impact information on Picovir


Chemical compound and disease context of Picovir


Biological context of Picovir

  • In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients [11].
  • To enhance the oral bioavailability of pleconaril, coadministration with a fat-containing meal is recommended [12].
  • Results revealed statistically significant reductions in viral shedding in nasal secretions (P<.001), nasal mucus production (P=.004), and total respiratory illness symptom scores (P=.013) in pleconaril-treated as compared with placebo-treated subjects [8].
  • Attenuated virulence of pleconaril-resistant coxsackievirus B3 variants [13].
  • A resistant cDNA-generated CVB3 became pleconaril-susceptible after accepting parts from the genome region encoding Ile-1092 into its capsid [14].

Anatomical context of Picovir


Associations of Picovir with other chemical compounds

  • First, the authors briefly described costs, risks, and possible symptomatic benefits of 4 treatment scenarios, based on evidence regarding vitamin C, echinacea, zinc, and pleconaril, an antiviral [15].
  • A greater volume of distribution (Vd) has been observed in the neonate compared with the adult for nelfinavir, nevirapine and pleconaril [16].
  • A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol [17].

Gene context of Picovir

  • Oral pleconaril increased intestinal and hepatic CYP3A activity [18].
  • Duration of pleconaril effect on cytochrome p450 3a activity in healthy adults using the oral biomarker midazolam [18].
  • The objective of this study was to evaluate the duration of oral pleconaril (a picornavirus inhibitor) effect on intestinal and hepatic cytochrome P450 (P450) 3A activity as assessed by oral midazolam [18].

Analytical, diagnostic and therapeutic context of Picovir

  • Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials [19].
  • Further, amino acid changes observed in reduced susceptibility variant viruses recovered from patients enrolled in clinical trials with pleconaril were distinct from those that confer natural phenotypic resistance to the drug [3].
  • Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography [11].
  • Ten independently derived pleconaril-resistant variants of coxsackievirus B3 were isolated from cell culture [13].
  • We report the results of a randomized two-way crossover study designed to characterize the disposition of a single dose (200 mg) of pleconaril oral solution in fed and fasting humans [12].


  1. Viral encephalitis: familiar infections and emerging pathogens. Whitley, R.J., Gnann, J.W. Lancet (2002) [Pubmed]
  2. Structural and virological studies of the stages of virus replication that are affected by antirhinovirus compounds. Zhang, Y., Simpson, A.A., Ledford, R.M., Bator, C.M., Chakravarty, S., Skochko, G.A., Demenczuk, T.M., Watanyar, A., Pevear, D.C., Rossmann, M.G. J. Virol. (2004) [Pubmed]
  3. VP1 sequencing of all human rhinovirus serotypes: insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds. Ledford, R.M., Patel, N.R., Demenczuk, T.M., Watanyar, A., Herbertz, T., Collett, M.S., Pevear, D.C. J. Virol. (2004) [Pubmed]
  4. Enteroviral meningitis: natural history and outcome of pleconaril therapy. Desmond, R.A., Accortt, N.A., Talley, L., Villano, S.A., Soong, S.J., Whitley, R.J. Antimicrob. Agents Chemother. (2006) [Pubmed]
  5. Treatment of ALS with pleconaril. Ansevin, C.F. Neurology (2001) [Pubmed]
  6. Relationship of pleconaril susceptibility and clinical outcomes in treatment of common colds caused by rhinoviruses. Pevear, D.C., Hayden, F.G., Demenczuk, T.M., Barone, L.R., McKinlay, M.A., Collett, M.S. Antimicrob. Agents Chemother. (2005) [Pubmed]
  7. A fatal case of coxsackievirus B4 meningoencephalitis. Cree, B.C., Bernardini, G.L., Hays, A.P., Lowe, G. Arch. Neurol. (2003) [Pubmed]
  8. Clinical activity of pleconaril in an experimentally induced coxsackievirus A21 respiratory infection. Schiff, G.M., Sherwood, J.R. J. Infect. Dis. (2000) [Pubmed]
  9. Human rhinovirus capsid dynamics is controlled by canyon flexibility. Reisdorph, N., Thomas, J.J., Katpally, U., Chase, E., Harris, K., Siuzdak, G., Smith, T.J. Virology (2003) [Pubmed]
  10. Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man. MacLennan, C., Dunn, G., Huissoon, A.P., Kumararatne, D.S., Martin, J., O'Leary, P., Thompson, R.A., Osman, H., Wood, P., Minor, P., Wood, D.J., Pillay, D. Lancet (2004) [Pubmed]
  11. Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Pediatric Pharmacology Research Unit Network. Kearns, G.L., Abdel-Rahman, S.M., James, L.P., Blowey, D.L., Marshall, J.D., Wells, T.G., Jacobs, R.F. Antimicrob. Agents Chemother. (1999) [Pubmed]
  12. Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution and effect of food. Abdel-Rahman, S.M., Kearns, G.L. Antimicrob. Agents Chemother. (1998) [Pubmed]
  13. Attenuated virulence of pleconaril-resistant coxsackievirus B3 variants. Groarke, J.M., Pevear, D.C. J. Infect. Dis. (1999) [Pubmed]
  14. Susceptibility of coxsackievirus B3 laboratory strains and clinical isolates to the capsid function inhibitor pleconaril: antiviral studies with virus chimeras demonstrate the crucial role of amino acid 1092 in treatment. Schmidtke, M., Hammerschmidt, E., Schüler, S., Zell, R., Birch-Hirschfeld, E., Makarov, V.A., Riabova, O.B., Wutzler, P. J. Antimicrob. Chemother. (2005) [Pubmed]
  15. Using benefit harm tradeoffs to estimate sufficiently important difference: the case of the common cold. Barrett, B., Brown, R., Mundt, M., Dye, L., Alt, J., Safdar, N., Maberry, R. Medical decision making : an international journal of the Society for Medical Decision Making. (2005) [Pubmed]
  16. Pharmacokinetics of antivirals in neonate. Pacifici, G.M. Early Hum. Dev. (2005) [Pubmed]
  17. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Hayden, F.G., Herrington, D.T., Coats, T.L., Kim, K., Cooper, E.C., Villano, S.A., Liu, S., Hudson, S., Pevear, D.C., Collett, M., McKinlay, M. Clin. Infect. Dis. (2003) [Pubmed]
  18. Duration of pleconaril effect on cytochrome p450 3a activity in healthy adults using the oral biomarker midazolam. Ma, J.D., Nafziger, A.N., Rhodes, G., Liu, S., Bertino, J.S. Drug Metab. Dispos. (2006) [Pubmed]
  19. Oral pleconaril treatment of picornavirus-associated viral respiratory illness in adults: efficacy and tolerability in phase II clinical trials. Hayden, F.G., Coats, T., Kim, K., Hassman, H.A., Blatter, M.M., Zhang, B., Liu, S. Antivir. Ther. (Lond.) (2002) [Pubmed]
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