Abstract
A series of mercaptan compounds were studied with respect to their ability to inhibit the growth of poliovirus in cultured cells. Of the compounds tested only d-penicillamine possessed antiviral activity. There was no direct effect on the virus itself, nor were the processes of adsorption, penetration and uncoating, or virus-induced “shut-off” of host cell protein synthesis inhibited. At concentrations where there was no effect on host cell RNA or protein synthesis, d-penicillamine caused a marked inhibition of virus-specific RNA and protein synthesis. Although much reduced, the relative concentrations of single-stranded and double-stranded viral RNA synthesized in the presence of d-penicillamine was unchanged. Similarly, all apparent precursor and cleavage product proteins could be synthesized in the presence of the drug. The inhibitory effect was reversible, after a lag of 1.5 to 2 h after removal of the drug, and normal yields of virus could be obtained. The structural and functional properties of d-penicillamine are discussed in relation to requirements for anti-polioviral activity.
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- Baltimore D., Girard M., Darnell J. E. Aspects of the synthesis of poliovirus RNA and the formation of virus particles. Virology. 1966 Jun;29(2):179–189. doi: 10.1016/0042-6822(66)90024-9. [DOI] [PubMed] [Google Scholar]
- Baum S. G., Horwitz M. S., Maizel J. V., Jr Studies of the mechanism of enhancement of human adenovirus infection in monkey cells by simian virus 40. J Virol. 1972 Aug;10(2):211–219. doi: 10.1128/jvi.10.2.211-219.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CHRISTIAN C. L. RHEUMATOID ARTHRITIS--ETIOLOGIC CONSIDERATIONS. Arthritis Rheum. 1964 Oct;7:455–466. doi: 10.1002/art.1780070502. [DOI] [PubMed] [Google Scholar]
- CRAWHALL J. C., SCOWEN E. F., WATTS R. W. Effect of penicillamine on cystinuria. Br Med J. 1963 Mar 2;1(5330):588–590. doi: 10.1136/bmj.1.5330.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CROWTHER D., MELNICK J. L. Studies of the inhibitory action of guanidine on poliovirus multiplication in cell cultures. Virology. 1961 Sep;15:65–74. doi: 10.1016/0042-6822(61)90078-2. [DOI] [PubMed] [Google Scholar]
- Gessa G. L., Loddo B., Brotzu G., Schivo M. L., Tagliamonte A., Spanedda A., Bo G., Ferrari W. Selective inhibition of poliovirus growth by d-Penicillamine in vitro. Virology. 1966 Dec;30(4):618–622. doi: 10.1016/0042-6822(66)90166-8. [DOI] [PubMed] [Google Scholar]
- JAFFE I. A., ALTMAN K., MERRYMAN P. THE ANTIPYRIDOXINE EFFECT OF PENICILLAMINE IN MAN. J Clin Invest. 1964 Oct;43:1869–1873. doi: 10.1172/JCI105060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobson M. F., Baltimore D. Polypeptide cleavages in the formation of poliovirus proteins. Proc Natl Acad Sci U S A. 1968 Sep;61(1):77–84. doi: 10.1073/pnas.61.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaffe I. A. The treatment of rheumatoid arthritis and necrotizing vasculitis with penicillamine. Arthritis Rheum. 1970 Jul-Aug;13(4):436–443. doi: 10.1002/art.1780130412. [DOI] [PubMed] [Google Scholar]
- KUCHINSKAS E. J., HORVATH A., DU VIGNEAUD V. An anti-vitamin B6 action of L-penicillamine. Arch Biochem Biophys. 1957 May;68(1):69–75. doi: 10.1016/0003-9861(57)90327-2. [DOI] [PubMed] [Google Scholar]
- La Colla P., Marcialis M. A., Mereu G. P., Loddo B. Specific inhibition of poliovirus induced blockade of cell protein synthesis by a thiopyrimidine derivative. J Gen Virol. 1972 Oct;17(1):13–18. doi: 10.1099/0022-1317-17-1-13. [DOI] [PubMed] [Google Scholar]
- Nimni M. E., Bavetta L. A. Collagen defect induced by penicillamine. Science. 1965 Nov 12;150(3698):905–907. doi: 10.1126/science.150.3698.905. [DOI] [PubMed] [Google Scholar]
- Penman S., Summers D. Effects on host cell metabolism following synchronous infection with poliovirus. Virology. 1965 Dec;27(4):614–620. doi: 10.1016/0042-6822(65)90187-x. [DOI] [PubMed] [Google Scholar]
- Studier F. W. Analysis of bacteriophage T7 early RNAs and proteins on slab gels. J Mol Biol. 1973 Sep 15;79(2):237–248. doi: 10.1016/0022-2836(73)90003-x. [DOI] [PubMed] [Google Scholar]
- Summers D. F., Maizel J. V., Jr, Darnell J. E., Jr Evidence for virus-specific noncapsid proteins in poliovirus-infected HeLa cells. Proc Natl Acad Sci U S A. 1965 Aug;54(2):505–513. doi: 10.1073/pnas.54.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WALSHE J. M. Disturbances of aminoacid metabolism following liver injury; a study by means of paper chromatography. Q J Med. 1953 Oct;22(88):483–505. [PubMed] [Google Scholar]