A series of ring expanded nucleoside (REN) analogues were synthesized and screened for inhibition of cellular RNA helicase activity and human immunodeficiency virus type 1 (HIV-1) replication. We identified two compounds, 1 and 2, that inhibited the ATP dependent activity of human RNA helicase DDX3. Compounds 1 and 2 also suppressed HIV-1 replication in T cells and monocyte-derived macrophages. Neither compound at therapeutic doses was significantly toxic in ex vivo cell culture or in vivo in mice. Our findings provide proof-of-concept that a cellular factor, an RNA helicase, could be targeted for inhibiting HIV-1 replication.
A series of ring expanded nucleoside (n class="Gene">REN) analogues were synthesized and screened for inhibition of cellular RNA helicase activity and human immunodeficiency virus type 1 (HIV-1) replication. We identified two compounds, 1 and 2, that inhibited the ATP dependent activity of human RNA helicaseDDX3. Compounds 1 and 2 also suppressed HIV-1 replication in T cells and monocyte-derived macrophages. Neither compound at therapeutic doses was significantly toxic in ex vivo cell culture or in vivo in mice. Our findings provide proof-of-concept that a cellular factor, an RNA helicase, could be targeted for inhibiting HIV-1 replication.
Authors: James J Crute; Christine A Grygon; Karl D Hargrave; Bruno Simoneau; Anne-Marie Faucher; Gordon Bolger; Philip Kibler; Michel Liuzzi; Michael G Cordingley Journal: Nat Med Date: 2002-04 Impact factor: 53.440
Authors: Peter Borowski; Johanna Deinert; Sarah Schalinski; Maria Bretner; Krzysztof Ginalski; Tadeusz Kulikowski; David Shugar Journal: Eur J Biochem Date: 2003-04
Authors: Atul Kondaskar; Shilpi Kondaskar; James C Fishbein; Brandon A Carter-Cooper; Rena G Lapidus; Mariola Sadowska; Martin J Edelman; Ramachandra S Hosmane Journal: Bioorg Med Chem Date: 2012-12-11 Impact factor: 3.641
Authors: Atul Kondaskar; Shilpi Kondaskar; Raj Kumar; James C Fishbein; Nidal Muvarak; Rena G Lapidus; Mariola Sadowska; Martin J Edelman; Guus M Bol; Farhad Vesuna; Venu Raman; Ramachandra S Hosmane Journal: ACS Med Chem Lett Date: 2010-12-31 Impact factor: 4.345