Inhibition of Moloney murine leukemia virus replication by tyrphostins, tyrosine kinase inhibitors.
We have previously shown that topoisomerase I (topo I) antagonist inhibited retrovirus replication. Since tyrphostins, synthetic compounds and protein tyrosine kinases (PTKs) blockers, inhibited topo I activity (manuscript in preparation) we examined their ability to inhibit Moloney murine leukemia virus (Mo-MuLV) replication. We found that non-cytotoxic doses of tyrphostin derivatives (AG-555, AG-18) blocked or substantially reduced Mo-MuLV replication in acute or chronically infected NIH/3T3 cells. Our experiments suggest that the antiviral effect of these tyrphostin derivatives was not the result of antiproliferative activity. However, the tyrphostin derivatives used in our present investigation differ in their ability to inhibit Mo-MuLV replication. Furthermore, as expected from stereospecific competitive inhibitors, the antiviral effect is not a general characteristic of all tyrphostin derivatives, since AG-213 does not affect Mo-MuLV replication. Our results indicate that these tyrphostin derivatives may represent a novel class of antiretroviral drugs.
Esther
A
A
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Iftach
S
S
Esther
P
P
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015151:Immunoblotting; D051379:Mice; D008979:Moloney murine leukemia virus / Q000187:drug effects* / Q000502:physiology; D009570:Nitriles / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020032:Tyrphostins; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001597:Benzylidene Compounds; D002396:Catechols; D009570:Nitriles; D020032:Tyrphostins; C095713:alpha-cyano-(3,4-dihydroxy)-N-(3-phenylpropyl)cinnamide; C060152:tyrphostin 47; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23