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Nucleosides and Nucleotides Volume 18, 1999 - Issue 4-5
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III. Phosphorylated Molecules and Pronucleotides

Antiviral Activity and Resistance Profile of Phosphazid - A Novel Prodrug of AZT

John Machado McGill University AIDS Centre, Jewish General Hospital, 3755 C[obreve]te-Ste-Catherine Road, Montreal (Quebec), CANADA, H3T 1E2
,
Horacio Salomon McGill University AIDS Centre, Jewish General Hospital, 3755 C[obreve]te-Ste-Catherine Road, Montreal (Quebec), CANADA, H3T 1E2
,
Maureen Oliveira McGill University AIDS Centre, Jewish General Hospital, 3755 C[obreve]te-Ste-Catherine Road, Montreal (Quebec), CANADA, H3T 1E2
,
Christos Tsoukas McGill University AIDS Centre, Jewish General Hospital, 3755 C[obreve]te-Ste-Catherine Road, Montreal (Quebec), CANADA, H3T 1E2
,
Alexander A. Krayevsky Engelhardt Institute, Russian Academy of Sciences, Moscow, Russia
&
Mark A. Wainberg McGill University AIDS Centre, Jewish General Hospital, 3755 C[obreve]te-Ste-Catherine Road, Montreal (Quebec), CANADA, H3T 1E2
Pages 901-906 | Published online: 04 Oct 2006
 
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Abstract

Both AZT and its novel 5′-hydrogen phosphonate derivative, Phosphazid, possess similar in vitro activity and resistance profiles. Experiments involving AZT-resistant virus isolates revealed a strong correlation between resistance to AZT and cross-resistance to Phosphazid. In vitro selection for resistance to Phosphazid yielded viruses that were about 15-fold less sensitive than wild-type virus to this drug. Sequencing of the reverse transcriptase region of seven Phosphazid-selected viruses revealed a single codon mutation, D67N, that is associated with resistance to AZT.

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