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5. Modulation of human immunodeficiency virus type I synergistic inhibition by reverse transcriptase mutations

Author

Basavapathruni, Aravind, Vingerhoets, Johan, De Bethune, Marie-Pierre, Chung, Raymond, Bailey, Christopher M., Kim, Jiae, and Anderson, Karen S.

Subjects
HIV (Viruses) -- Genetic aspects, Nucleosides -- Chemical properties, Nucleosides -- Structure, Reverse transcriptase -- Chemical properties, Gene mutations -- Research, Biological sciences, Chemistry
Abstract

Modulation of human immunodeficiency virus type I synergistic inhibition by reverse transcriptase (RT) mechanism was examined. The synergy between the anti-human immunodeficiency virus type I (HIV) nucleoside RT inhibitors (NRTIs) and nonnucloside RT inhibitors (NNRTIs) results from a general mechanism in which NNRTIs inhibit ATP-mediated removal of NRTIs from chain-terminated primers. This requires NNRTIs that are potent against wild type virus and possess favorable activity profiles against clinically relevant mutations.

Published
2006

8. Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 gag-pol

Author

Figueiredo, Anna, Moore, Katie L., Mak, Johnson, Sluis-Cremer, Nicolas, de Bethune, Marie-Pierre, Tachedjian, Gilda, Figueiredo, Anna, Moore, Katie L., Mak, Johnson, Sluis-Cremer, Nicolas, de Bethune, Marie-Pierre, and Tachedjian, Gilda

Abstract

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) target HIV-1 reverse transcriptase (RT) by binding to a pocket in RT that is close to, but distinct, from the DNA polymerase active site and prevent the synthesis of viral cDNA. NNRTIs, in particular, those that are potent inhibitors of RT polymerase activity, can also act as chemical enhancers of the enzyme's inter-subunit interactions. However, the consequences of this chemical enhancement effect on HIV-1 replication are not understood. Here, we show that the potent NNRTIs efavirenz, TMC120, and TMC125, but not nevirapine or delavirdine, inhibit the late stages of HIV-1 replication. These potent NNRTIs enhanced the intracellular processing of Gag and Gag-Pol polyproteins, and this was associated with a decrease in viral particle production from HIV-1-transfected cells. The increased polyprotein processing is consistent with premature activation of the HIV-1 protease by NNRTI-enhanced Gag-Pol multimerization through the embedded RT sequence. These findings support the view that Gag-Pol multimerization is an important step in viral assembly and demonstrate that regulation of Gag-Pol/Gag-Pol interactions is a novel target for small molecule inhibitors of HIV-1 production. Furthermore, these drugs can serve as useful probes to further understand processes involved in HIV-1 particle assembly and maturation.

Published
2006

10. Design of HIV-1 Protease Inhibitors Active on Multidrug-Resistant Virus

Author

Surleraux, Dominique L. N. G., primary, de Kock, Herman A., additional, Verschueren, Wim G., additional, Pille, Geert M. E., additional, Maes, Louis J. R., additional, Peeters, Anik, additional, Vendeville, Sandrine, additional, De Meyer, Sandra, additional, Azijn, Hilde, additional, Pauwels, Rudi, additional, de Bethune, Marie-Pierre, additional, King, Nancy M., additional, Prabu-Jeyabalan, Moses, additional, Schiffer, Celia A., additional, and Wigerinck, Piet B. T. P., additional

Published
2005
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11. Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

Author

Surleraux, Dominique L. N. G., primary, Tahri, Abdellah, additional, Verschueren, Wim G., additional, Pille, Geert M. E., additional, de Kock, Herman A., additional, Jonckers, Tim H. M., additional, Peeters, Anik, additional, De Meyer, Sandra, additional, Azijn, Hilde, additional, Pauwels, Rudi, additional, de Bethune, Marie-Pierre, additional, King, Nancy M., additional, Prabu-Jeyabalan, Moses, additional, Schiffer, Celia A., additional, and Wigerinck, Piet B. T. P., additional

Published
2004
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13. Evolution of anti-HIV drug candidates. Part 3: diarylpyrimidine (DAPY) analogues

Author

Ludovici, Donald W., De Corte, Bart L., Kukla, Michael J., Ye, Hong, Ho, Chih Y., Lichtenstein, Mark A., Kavash, Robert W., Andries, Koen, de Béthune, Marie-Pierre, Azijn, Hilde, Pauwels, Rudi, Lewi, Paul J., Heeres, Jan, Koymans, Lucien M.H., de Jonge, Marc R., Van Aken, Koen J.A., Daeyaert, Frederik F.D., Das, Kalyan, Arnold, Edward, and Janssen, Paul A.J.

Published
2001
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15. Evolution of Anti-HIV Drug CandidatesPart 2: Diaryltriazine (DATA) Analogues

Author

Ludovici, Donald W., Kavash, Robert W., Kukla, Michael J., Ho, Chih Y., Ye, Hong, De Corte, Bart L., Andries, Koen, de Béthune, Marie-Pierre, Azijn, Hilde, Pauwels, Rudi, Moereels, Henry E.L., Heeres, Jan, Koymans, Lucien M.H., de Jonge, Marc R., Van Aken, Koen J.A., Daeyaert, Frederik F.D., J. Lewi, Paul, Das, Kalyan, Arnold, Edward, and Janssen, Paul A.J.

Published
2001
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16. Characterisation of the Binding of Virginiamycin S to <em>Escherichia coli</em> Ribosomes.

Author

de Bethune, Marie-Pierre and Nierhaus, Knud H.

Subjects
*ESCHERICHIA coli, *RIBOSOMES, *BIOCHEMISTRY, *BACTERIOLOGY, *MOLECULAR microbiology, *MOLECULAR biology, *BIOLOGY
Abstract

Virginiamycin S is an inhibitor of protein synthesis in vivo. In this paper we show by equilibrium dialysis that it binds specifically to the 50-S subunit of Escherichia coli ribosomes, with one binding site per subunit. This binding is not altered by the presence of chloramphenicol, tetracycline or puromycin but is competed for by erythromycin. Using the splitting-reconstitution method, it could be demonstrated that protein L16 is absolutely required for the binding of virginiamycin S to the 50-S subunit. [ABSTRACT FROM AUTHOR]

Published
1978
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20. Principles of Science: Pharmacology

Author

Editors of Salem Press and Editors of Salem Press

Subjects
Pharmacology
Abstract

This new resource introduces students and researchers to the fundamentals of pharmacology using easy-to-understand language, to provide a solid background, and help readers develop a deeper understanding and appreciation of this important and evolving subject.

Published
2019

21. Salem Health: Infectious Diseases and Conditions, Second Edition

Author

H. Bradford Hawley and H. Bradford Hawley

Subjects
Communicable diseases--Encyclopedias
Abstract

An A-Z encyclopedia covering all aspects of infectious diseases and their prevention, offering historical and technical background with a balanced discussion of discoveries, developments, and prognoses.

Published
2019

22. Salem Health: Infectious Diseases & Conditions

Author

H. Bradford Hawley and H. Bradford Hawley

Subjects
Communicable diseases, Communicable diseases--Encyclopedias
Abstract

Covers all aspects of infectious diseases and their prevention, offering historical and technical background with a balanced discussion of discoveries, developments, and prognoses.

Published
2012

23. Metabolites : A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Author

Parker, Philip M., Parker, James N., Parker, Philip M., and Parker, James N.

Subjects
Metabolites--Computer network resources, Metabolites--Bibliography, Metabolites--Electronic information resources, Metabolites--Information resources, Metabolites--Dictionaries
Abstract

This is a 3-in-1 reference book. It gives a complete medical dictionary covering hundreds of terms and expressions relating to metabolites. It also gives extensive lists of bibliographic citations. Finally, it provides information to users on how to update their knowledge using various Internet resources. The book is designed for physicians, medical students preparing for Board examinations, medical researchers, and patients who want to become familiar with research dedicated to metabolites. If your time is valuable, this book is for you. First, you will not waste time searching the Internet wh.

Published
2004

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