Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Effectiveness of commercial inhibitors against subtype F HIV-1 protease

Full text
Krauchenco, Sandra [1] ; Martins, Nadia H. [1] ; Sanches, Mario [2] ; Polikarpov, Igor [1]
Total Authors: 4
[1] Univ Sao Paulo, IFSC, BR-13560970 Sao Carlos, SP - Brazil
[2] Lab Nacl Luz Sincrotron, BR-13084971 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 24, n. 3, p. 638-645, 2009.
Web of Science Citations: 4

Subtype F wild type HIV protease has been kinetically characterized using six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3 and acetylpepstatin. We also obtained kinetic parameters for two multi-resistant proteases (one of subtype B and one of subtype F) harboring primary and secondary mutations selected by intensive treatment with ritonavir/nelfinavir. This newly obtained biochemical data shows that all six studied commercially available protease inhibitors are significantly less effective against subtype F HIV proteases than against HIV proteases of subtype B, as judged by increased K(i) and biochemical fitness (vitality) values. Comparison with previously reported kinetic values for subtype A and C HIV proteases show that subtype F wild type proteases are significantly less susceptible to inhibition. These results demonstrate that the accumulation of natural polymorphisms in subtype F proteases yields catalytically more active enzymes with a large degree of cross-resistance, which thus results in strong virus viability. (AU)

FAPESP's process: 06/00182-8 - Structural biophysics of nuclear receptors and related proteins
Grantee:Igor Polikarpov
Support type: Research Projects - Thematic Grants
FAPESP's process: 99/03387-4 - Structural studies of the proteins using synchrotron light
Grantee:Igor Polikarpov
Support type: Research Projects - Thematic Grants