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[How proviral DNA is integrated into the host cell DNA and how this process can be inhibited].

Abstract：

:The HIV replication cycle passes through a stage of integrating proviral DNA into the cell's DNA. In this process, the viral enzyme, integrase, catalyses two reactions. The first reaction, which seems to occur in the cytoplasm, involves 3'-end processing, in which two nucleotides are removed from the 3' ends of the viral DNA by integrase. The second reaction, which occurs in the nucleus, involves the strand transfer reaction, catalyzed by integrase, in which the recessed 3' ends of the viral DNA are joined to the protruding 5' ends in the target DNA. Although this activity has not yet been completely defined and the structure of the active form of integrase, probably a tetramer, has not been resolved, drugs of the diketoacid (DKA) family have been found. These drugs are highly potent inhibitors of the second phase, the strand transfer reaction. Through a series of optimizations, a highly effective molecule for clinical use, raltegravir, has been achieved. The present article provides a summary of basic knowledge on integrase, as well as the activity and the modes of inhibition of this enzyme. Also discussed is the reduced, but nevertheless real, development of resistance to raltegravir, requiring second-generation integrase inhibitors to be designed.

journal_name

Enferm Infecc Microbiol Clin

journal_title

Enfermedades infecciosas y microbiologia clinica

authors

Mirambeau G

doi

10.1016/s0213-005x(08)76567-4

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

11-6

eissn

0213-005X

issn

1578-1852

pii

S0213-005X(08)76567-4

journal_volume

26 Suppl 12

pub_type

杂志文章,评审

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