Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase.
Yudong Quan,Dimitrios Motakis,Robert W. Buckheit,Ze-Qi Xu,Michael T. Flavin,Michael A. Parniak,Mark A. Wainberg +6 more
Reads0
Chats0
TLDR
Tissue culture results indicated that the combination of (+)-calanolide A and nevirapine possessed an additive to weakly synergistic effect in blocking replication of HIV-1 in tissue culture, suggesting that (+)-Calanolide B and ne virapine might have rationale as a combination therapy for HIV disease.Abstract:
We have tested both wild-type and drug-resistant mutated, recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) molecules for sensitivity to each of two non-nucleoside ...read more
Citations
More filters
Journal ArticleDOI
Plant-Derived Leading Compounds for Chemotherapy of Human Immunodefiency Virus (HIV) Infection-An Update (1998-2007)
TL;DR: The following antiviral chemical classes are discussed in detail: alkaloids, carbohydrates, coumarins, flavonoids, lignans, phenolics, proteins, quinones/xanthones, tannins and terpenes.
Journal ArticleDOI
Recent advances in anti-HIV natural products
TL;DR: This review covers the recent advances in anti-HIV natural products of various origins and chemical classes from 2004 to April 2010, with around 160 compounds discussed and 141 references cited.
Journal ArticleDOI
Safety and Pharmacokinetics of Single Doses of (+)-Calanolide A, a Novel, Naturally Occurring Nonnucleoside Reverse Transcriptase Inhibitor, in Healthy, Human Immunodeficiency Virus-Negative Human Subjects
Terri Creagh,Jon L. Ruckle,Dwain T. Tolbert,Jeremy Giltner,David A. Eiznhamer,Bipul Dutta,Michael T. Flavin,Ze-Qi Xu +7 more
TL;DR: Levels of (+)-calanolide A in human plasma were higher than would have been predicted from animal studies, yet the safety profile remained benign, and although raw plasma drug levels were higher in women than in men, when doses were normalized for body mass, the pharmacokinetic profiles were virtually identical with those observed for males.
Journal ArticleDOI
Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile.
Hai Xue,Xiaofan Lu,Purong Zheng,Li Liu,Chunyan Han,Jinping Hu,Zijie Liu,Tao Ma,Yan Li,Lin Wang,Zhiwei Chen,Gang Liu +11 more
TL;DR: In this paper, a new compound, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC50 = 7.4 nM, SI = 1417), was reported.
Book ChapterDOI
Inhibitors of HIV-1 reverse transcriptase.
TL;DR: In this paper, the authors describe the current clinically used RT inhibitors, outlining mechanisms of action as well as factors in HIV resistance to these drugs, and some promising new pipeline RT inhibitors are discussed, including compounds directed at novel RT targets not addressed by current RT therapeutics.
References
More filters
Journal ArticleDOI
HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy
TL;DR: It would be premature to alter any treatment protocols for HIV-infected individuals at present, as it cannot be determined from this small sample of patients whether development of a less sensitive virus phenotype results in clinical resistance.
Journal ArticleDOI
Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides.
Hiroaki Mitsuya,Samuel Broder +1 more
TL;DR: In this paper, the capacity of purine and pyrimidine nucleoside derivatives to inhibit the infectivity and cytopathic effect of human T-lymphotropic virus type III in vitro was tested.
Nevirapine Resistance Mutations ofHumanImmunodeficiency VirusType1Selected during Therapy
Douglas D. Richman,Diane V. Havlir,David Looney,Caroline Ignacio,John L. Sullivan,Cheng-Kon Shih,Maureen Myers,Johanna A. Griffin +7 more
Abstract: Drug susceptibility and mutations in the reverse transcriptase (RT) gene were analyzed with 167 virus isolates from 38 patients treated with nevirapine, a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT. Resistant isolates emerged quickly and uniformly in all patients administered nevirapine either as monotherapy or in combination with zidovudine (AZT). Resistance developed as early as 1 week, indicating rapid turnover of the virus population. The development of resistance was associated with the loss of antiviral drug activity as measured by CD4 lymphocyte counts and levels of HIV p24 antigen and RNA in serum. In addition to mutations at amino acid residues 103, 106, and 181 that had been identified by selection in cell culture, mutations at residues 108, 188, and 190 were also found in the patient isolates. Sequences from patient clones documented cocirculating mixtures of populations of different mutants. The most common mutation with monotherapy, tyrosine to cysteine at residue 181, was prevented from emerging by coadministration of AZT, which resulted in the selection of alternative mutations. The observations documented that, under selective drug pressure, the circulating virus population can change rapidly, and many alternative mutants can emerge, often in complex mixtures. The addition of a second RT inhibitor, AZT, significantly altered the pattern of mutations in the circulating population of HIV.
Journal ArticleDOI
The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum.
Yoel Kashman,Kirk R. Gustafson,Richard W. Fuller,John H. Cardellina,James B. McMahon,Michael J. Currens,Robert W. Buckheit,Stephen H. Hughes,Gordon M. Cragg,Michael R. Boyd +9 more
TL;DR: Calanolide A was active not only against the AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant A17 strain, which was of particular interest since the A17 virus is highly resistant to previously known HIV- 1 specific, non-nucleoside RT inhibitors.
Journal ArticleDOI
Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors
TL;DR: The data suggest that an inhibitor combining the functionalities of a nonnucleoside inhibitor and a nucleotide analog could bind very tightly and specifically to reverse transcriptase and could be effective in the treatment of AIDS.