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(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

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Author(s):
Krauchenco, Sandra [1] ; Martins, Nadia H. [1] ; Sanches, Mario [2] ; Polikarpov, Igor [1]
Total Authors: 4
Affiliation:
[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
Abstract

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