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Human Immunodeficiency Virus Reverse Transcriptase (Hardcover, 2013 ed.)
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Human Immunodeficiency Virus Reverse Transcriptase (Hardcover, 2013 ed.)
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The Reverse Transcriptase (RT) of Human Immunodeficiency Virus Type
1 (HIV-1) arguably ranks amongst one of the most extensively
studied retroviral enzymes. Heterologous expression and
purification of HIV-1 RT in the early eighties, approval of the
first nucleoside analogue RT inhibitor (NRTI) in 1987, discovery of
resistance to RT inhibitors, approval of the first non-nucleoside
analogue RT inhibitor (NNRTI) in 1996 and the various crystal
structures of RT with and without bound substrate(s) and/or
inhibitors represent only a few of the important milestones that
describe the a bench-to-bedside success in the continuing effort to
combat HIV-1 infection and its consequences. Nucleoside and
nonnucleoside RT inhibitors remain important components in
frequently used drug regimens to treat the infection. RT inhibitors
also play important roles in recently validated strategies to
prevent transmission of the virus. The relevance of HIV-1 RT as a
drug target has simultaneously triggered interest in basic research
studies aimed at providing a more detailed understanding of
interactions between proteins, nucleic acids, and small molecule
ligands in general terms. In light of the ever-growing knowledge on
structure and function of HIV-1 RT, this enzyme serves as a
valuable "model system" in efforts to develop novel experimental
tools and to explain biochemical processes. This monograph is
designed to provide an overview of important aspects in past and
current HIV-1 RT research, with focus on mechanistic aspects and
translation of knowledge into drug discovery and development. The
first section includes chapters with emphasis placed on the
coordination of the RT-associated DNA polymerase and ribonuclease H
(RNase H) activities. The second covers mechanisms of action and
future perspectives associated with NRTIs and NNRTIs, while the
third section includes chapters focusing on novel strategies to
target the RT enzyme. Chapters of the final part are intended to
discuss mechanisms involved in HIV variability and the development
of drug resistance. We hope that these contributions will stimulate
interest, and encourage research aimed at the development of novel
RT inhibitors. The lack of bona fide RNase H inhibitors with potent
antiviral activity provides an example for challenges and
opportunities in the field.
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