The effect of a novel inhibitor of aldehyde dehydrogenase on viral replication.
The effect of AMPAL (4-amino 4-methyl 2-pentyne 1-al), an inhibitor of aldehyde dehydrogenase, on adenovirus type 5 (Ad5) replication was studied. AMPAL at 2 x 10(-4) M clearly reduced the cytopathic effect on HeLa cells but had no effect on cell growth at this concentration. Viral adsorption, penetration and protein synthesis were not affected by adding AMPAL at 2 hr post infection. When viral DNA synthesized in the presence of AMPAL was investigated, no significant inhibition was observed on either synthesis or the physicochemical properties of the neosynthesized DNA. However, there was a 4-fold increase in the amount of condensed DNA. In addition, AMPAL inhibited intracellular viral production (40%) and brought about concomitant inhibition of virus release (70%) into the medium. The absence of a quantitative relationship between the inhibition of viral DNA synthesis on one hand and that of viral production on the other may imply that the antiviral effect of AMPAL is indirectly mediated by the action of the malondialdehyde which has accumulated on some, as not yet identified, membrane constituent.
Ogier
G
G
INSERM, Lyon, France.
Chantepie
J
J
Quash
G
G
Doutheau
A
A
Gore
J
J
Marion
C
C
D000260:Adenoviruses, Human / Q000187:drug effects / Q000472:pathogenicity; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000447:Aldehydes / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D014176:Protein Biosynthesis; D013816:Thermodynamics; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000447:Aldehydes; D004279:DNA, Viral; D014764:Viral Proteins; C059170:4-amino-4-methyl-2-pentyne-1-al; D008315:Malondialdehyde; D004247:DNA; D000444:Aldehyde Dehydrogenase