(-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human immunodeficiency virus type 1 and type 2 replication in vitro.
The (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3TC) was found to be a potent and selective inhibitor of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2) in vitro. We determined its antiviral activity against a number of laboratory strains of HIV-1 and HIV-2 in a range of CD4-bearing lymphocyte cell lines (mean 50% inhibitory concentration [IC50] range, 4 nM to 0.67 microM). 3TC was also active against a range of HIV-1 strains in peripheral blood lymphocytes (mean IC50 range, 2.5 to 90 nM). The IC50 for cytotoxicity in seven lymphocyte cell cultures, including human peripheral blood lymphocytes, ranged from 0.5 to 6 mM. 3TC had no detectable antiviral activity against a range of other viruses or in cells chronically infected with HIV-1 or HIV-2. The effects of time of addition of the compound and varying the multiplicity of infection on the antiviral activity of 3TC were determined. The results showed that 3TC is a potent and selective inhibitor of HIV-1 and HIV-2 replication in vitro.
Coates
J A
JA
Department of Virology, Glaxo Group Research Ltd., Middlesex, United Kingdom.
Cammack
N
N
Jenkinson
H J
HJ
Jowett
A J
AJ
Jowett
M I
MI
Pearson
B A
BA
Penn
C R
CR
Rouse
P L
PL
Viner
K C
KC
Cameron
J M
JM
D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016049:Didanosine / Q000494:pharmacology; D015726:Giant Cells / Q000187:drug effects; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase / Q000032:analysis; D014316:Tritium; D014779:Virus Replication / Q000187:drug effects; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015215:Zidovudine / Q000494:pharmacology
D014316:Tritium; D019259:Lamivudine; D015215:Zidovudine; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016049:Didanosine