Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “reverse transcriptase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,117 records · Page 62Linked to original sources
PubMed1991

Localization of a polynucleotide binding region in the HIV-1 reverse transcriptase: implications for primer binding.

Properties of primer recognition by purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) p66 homodimer have been investigated. Earlier studies had shown that RNA-directed DNA synthesis catalyzed by HIV-1 RT proceeds by an ordered mechanism in which template-primer combines with the free enzyme to form the first complex in the reaction scheme, and it was also shown that primer alone is a competitive inhibitor of template-primer. In this study, enzyme-primer binding has been further characterized utilizing pd(T)8 and pd(T)16 as model primers and UV cross-linking to covalently trap the enzyme-primer complexes. Competition experiments with several authentic primers, including tRNA(3Lys), indicate that pd(T)n binds to the kinetically significant primer binding site of RT. Salt reversal experiments suggested that the free energy of pd(T)n binding to RT has a large nonelectrostatic component. Binding of pd(T)n to p66-RT is not affected by dNTPs and does not require the presence of template. The site of UV cross-linking of pd(T)16 was localized to the NH2-terminal half of p66 by use of V8 protease hydrolysis and microsequencing. Our results indicate that a polynucleotide binding site is in close proximity to residues in the peptide comprising amino acids 195 approximately 300. This region could be either a single-stranded template or single-stranded primer binding site; however, we have documented the specificity of binding with oligonucleotides that act as primer in the in vitro DNA synthesis reaction. Therefore, this d(T)16 binding site may be part of a primer-binding groove within the HIV-1 reverse transcriptase.

Animals↗
PubMed1987

Inhibition of the reverse transcriptase from HIV by 3'-azido-3'-deoxythymidine triphosphate and its threo analogue.

3'-Azido-3'-deoxythymidine triphosphate (erythro) and its threo isomer were synthesized and investigated for their inhibition of HIV reverse transcriptase from virus isolate U 937/HTLV-III. The erythro isomer was a competitive inhibitor of the reaction directed by (rA)n(dT)12-18 and the Ki value was 0.0022 microM. The threo isomer was at least 100-fold less active. The inhibition was specific for dTMP incorporation, and dGMP incorporation using (rC)n(dG)12-18 as template/primer was not affected. The Km value for dTTP varied between 0.7 microM and 1.7 microM. Reverse transcriptase from nine HIV isolates were tested for inhibition by the erythro isomer and only slight differences in sensitivity were observed.

Antiviral Agents↗
PubMed1998

A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model.

HIV-1 reverse transcriptase (RT) is a key enzyme involved in the replication of the virus and is a potential target for therapeutic intervention following infection. Several drugs that inhibit the enzyme from acting have been discovered. These include nucleoside-analogue inhibitors such as AZT (zidovudine), ddI and ddC, and non-nucleoside inhibitors such as nevirapine and delavirdine. All of them, however have been found to be of limited clinical utility because the RT becomes rapidly resistant to them on account of point mutations in the enzyme. One way to partly overcome this limitation is to design an inhibitor that has interactions mainly with the backbone and the conserved residues of RT. Using a rational drug-design approach based on the high resolution X-ray crystal structure of the RT-nevirapine complex (1), and the specific design principles of peptides containing dehydro-Alanine (deltaAla) generated by our theoretical calculations, we present here the design of a peptide inhibitor of RT. Energy minimization and molecular modeling of the interaction of the designed pentapeptide with the nevirapine-binding site indicate that the inhibitor has 60% of its interactions with the conserved regions of RT as compared to 30% in the case of nevirapine, thus making it much less sensitive to mutations in the enzyme.

Computer Simulation↗
PubMed1998

Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives.

The carboxanilides are nonnucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT), of potential clinical importance. The compounds differ in potency and in their retention of potency in the face of drug resistance mutations. Whereas UC-84, the prototype compound, only weakly inhibits many RTs bearing single point resistance mutations, inhibition by UC-781 is little affected. It has been proposed that UC-38 and UC-781 may form quaternary complexes with RT at a site other than the known binding pocket of other NNIs. X-ray crystal structures of four HIV-1 RT-carboxanilide complexes (UC-10, UC-38, UC-84, and UC-781) reported here reveal that all four inhibitors bind in the usual NNI site, forming binary 1:1 complexes with RT in the absence of substrates with the amide/thioamide bond in cis conformations. For all four complexes the anilide rings of the inhibitors overlap aromatic rings of many other NNIs bound to RT. In contrast, the second rings of UC-10, UC-84, and UC-781 do not bind in equivalent positions to those of other "two-ring" NNIs such as alpha-APA or HEPT derivatives. The binding modes most closely resemble that of the structurally dissimilar NNI, Cl-TIBO, with a common hydrogen bond between each carboxanilide NH- group and the main-chain carbonyl oxygen of Lys101. The binding modes differ slightly between the UC-10/UC-781 and UC-38/UC-84 pairs of compounds, apparently related to the shorter isopropylmethanoyl substituents of the anilide rings of UC-38/UC-84, which draws these rings closer to residues Tyr181 and Tyr188. This in turn explains the differences in the effect of mutated residues on the binding of these compounds.

Anilides↗
PubMed1996

Isolation of an in vitro transmissible agent with reverse transcriptase activity from a blood donor with a borderline-positive HIV-1 serology for more than five years.

BACKGROUND: Reverse transcriptase (RT) is present in all infectious retrovirus particles. Sensitive RT tests should thus detect all such particles. A family of ultrasensitive RT tests, product-enhanced reverse transcriptase (PERT) assays, have been designed. Accumulated results show that (i) a first version of the PERT assay that uses microtiter/ELISA technology detects RT of only 3-11 retroviral particles, (ii) very different human and animal lenti- and oncoviruses are detected very sensitively, (iii) HIV-1 is detected as sensitively as with polymerase chain reaction (PCR) for viral RNA, and (iv) prevalence of elevated particle-associated RT in plasma of unselected Swiss blood donors was 1.9%. OBJECTIVE: To investigate whether the RT activity detected in one unselected donor with a chronically elevated level of the liver enzyme alanine aminotransferase and two selected donors with chronically indeterminate or borderline-positive HIV-1 serology was due to human immunodeficiency virus (HIV) or human T-cell leukemia virus (HTLV) infection. STUDY DESIGN: Blood samples were tested by PCR for viral DNA and/or RNA of HIV-1, HIV-2, HTLV-1, HTLV-2, hepatitis B and C virus. Serological tests and virus cultures were also employed. RESULTS: Infection with any of the above agents could not be demonstrated. Virus cultivation in one case of borderline-positive HIV-1 Western blot for more than 5 years yielded a peak of RT production that was repeatedly transmissible to fresh cells. CONCLUSIONS: The findings suggest the presence of an infectious RT-positive agent, probably different from HIV-1/2 or HTLV-1/2, in a healthy individual with chronically borderline-positive HIV-1 serology. The PERT assay may detect retroviruses currently undetectable by other tests. The use of more stringent Western blot interpretation guidelines other than those of CDC or WHO is strongly recommended.

Journal Article↗
PubMed1996

Evaluation of human immunodeficiency virus type 1 reverse transcriptase primer tRNA binding by fluorescence spectroscopy: specificity and comparison to primer/template binding.

A host cell-derived tRNA3Lys molecule is utilized by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) to prime DNA synthesis from the viral RNA genome. We performed fluorescence titration experiments to characterize the interaction between RT and its natural primer, tRNA3Lys, and to address RT's putative role in the required and specific packaging of tRNA3Lys into the budding virus. Titration of RT with tRNA3Lys resulted in a 30% maximal quenching of RT tryptophan fluorescence, from which a dissociation constant (Kd) of 57.6 +/- 7.5 nM was derived. Titration of RT with Escherichia coli tRNA2Glu, E. coli tRNA2Tyr, E. coli tRNALys, yeast tRNAPhe, or in vitro-synthesized human tRNA3Lys (no base modifications) resulted in similar fluorescence changes and Kd values as obtained for the natural tRNA3Lys. The specific interaction between RT and tRNA3Lys during viral assembly suggested by previous in vivo studies is therefore not present in the fully processed, in vitro form of RT. Other factors during viral assembly must therefore cooperate in the packaging of tRNA3Lys. The nonspecific and ionic strength dependent RT-tRNA interaction detected in the present studies suggests that the overall shape and charges of tRNA constitute recognition features for RT binding. The fluorescence of the wyebutine base contained on the anticodon loop of yeast tRNAPhe was found to increase upon RT binding, supporting speculation that RT interacts with the anticodon loop of tRNA. The individual tRNAs also displaced a fluorescent DNA primer/template (p/t) substrate from RT, indicating overlapping tRNA and p/t binding sites. Cubic fit evaluation of the displacement titrations allowed further assessment of the affinities of the two competing ligands. The presence of both overlapping and separate p/t and tRNA binding regions on RT was tested by examination of the affinity of a possible RT bisubstrate type inhibitor, containing motifs proposed to be essential for both tRNA and p/t binding. Reverse transcriptase was found to bind to the mutant tRNA 10-fold more tightly than to the unaltered tRNA (Kd = 4.5 +/- 1.0 and 44.6 +/- 6.6 nM, respectively). Further analyses revealed that the tighter affinity is probably due to a preferred p/t binding mode and not to one expected if separate tRNA and p/t binding regions are accessed simultaneously by the same molecule.

Base Sequence↗
PubMed1995

L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase.

The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the rapid selection of inhibitor-resistant viral variants. However, it may be possible to enhance the clinical utility of this inhibitor class by deriving compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of NNRTIs, the 1, 4-dihydro-2H-3, 1-benzoxazin-2-ones. L-743, 726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (Ki = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-7743, 7726 was found to be capable of inhibiting, with 95% inhibitory concentrations of < or = 1.5 microM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution. Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination of at least two RT amino acid substitutions. Studies of L-743, 726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good oral bioavailability and pharmacokinetics in humans.

Alkynes↗
PubMed2005

Synthesis and evaluation of double-prodrugs against HIV. Conjugation of D4T with 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine)-type reverse transcriptase inhibitors via the SATE prodrug approach.

This paper reports the synthesis and the antiviral activities of new double-prodrugs against HIV based on the known mixed SATE (S-acyl-2-thioethyl) prodrug approach. The monophosphate of the nucleoside reverse transcriptase inhibitor (NRTI) d4T was masked with one SATE group and one aromatic group through which a nonnucleoside reverse transcriptase inhibitor (NNRTI) was linked. Double-prodrug 1 was a hybrid between d4T monophosphate and the known NNRTI MKC-442, which were linked through a labile p-hydroxybenzoyl protection group in the N-3 position of MKC-442. Double-prodrugs 2 and 3 were conjugates between d4T monophosphate and the new NNRTIs 15 and 19 linked through a stable phenolic linker that was a part of the N-1 substituents of the NNRTIs. The double-prodrugs 1, 2, and 3 all had good activities against wild-type HIV-1, Y181C mutant, and also against a HIV-2 strain that was resistant to NNRTIs.

Cell Line↗
PubMed1994

Resistance pattern of human immunodeficiency virus type 1 reverse transcriptase to quinoxaline S-2720.

The human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline S-2720 showed a more-potent inhibitory effect on HIV-1-induced cytopathicity in CEM cells than either nevirapine, pyridinone L-697,661, bis-heteroarylpiperazine (BHAP) U-88204, TSAO ([2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4-amino-1",2"-oxathiole-2",2"-dioxide)-N3-ethylthymine, or 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4-benzodiazepin-2(I H)-one (TIBO) R82913. The quinoxaline derivative was also markedly more inhibitory to the mutant HIV-1 strains containing in their RT Ile-100, Asn-103, Ala-106, Lys-138, Cys-181, or His-188 substitutions than were the other HIV-1-specific RT inhibitors. Moreover, quinoxaline S-2720 totally prevented HIV-1 infection and emergence of drug-resistant mutant virus strains in CEM cell cultures at concentrations (i.e., 0.35 microM) that are 10- to 25-fold lower than those required for BHAP U-88204 and nevirapine to knock out the virus. Also, the concentration-response curve for S-2720 was markedly steeper than for BHAP and nevirapine, as reflected by the ratio of the 95% to the 50% antivirally effective concentration. Lower concentrations of quinoxaline dominantly lead to the appearance of the Ala-106 RT mutation, causing low-level resistance to the compound. At higher quinoxaline concentrations, the Glu-190 RT and/or the Cys-181 RT mutation is added to the Ala-106 mutation, whereas at the highest quinoxaline concentrations, the Ala-106 mutation tends to disappear from the virus pool, leaving the Glu-190 RT and Cys-181 RT mutations as the only mutations conferring high-level resistance to the compound.

Amino Acid Sequence↗
PubMed2005

[Inhibition of growth and proliferation of Hep-2 cells by targeting human telomerase reverse transcriptase mRNA using RNA interference technology].

OBJECTIVE: To investigate the effect of RNA interference by targeting human telomerase reverse transcriptase (hTERT) mRNA in the larynx cancer cell line, Hep-2. METHODS: The primary structures of hTERT cDNA were found in GenBank. Then the structure analysis were done according to RNAi strategy which determined the specific base sequences to design shRNA plasmid. Two types of plasmid, pshRNA1 and pshRNA2, involved in fluorescein gene were synthesized based on the specific base sequences. Control pshRNA3, a random sequence, and control pshRNA4, without additional specific sequence were also constructed. Cells were treated daily with pshRNA1-4 or normal culture medium respectively. The pshRNA1-3 was identified by electrophoresis. After administration of pshRNA1-4, fluorescence expression was detected by confocal microscopy, the expression of hTERT of the transfected cells was determined by Western blotting, telomerase activity was measured by TRAP-PCR ELISA, cell viability was determined by MTT assay, morphological changes and apoptosis were examined by inverted microscope and TUNEL respectively. RESULTS: There was a 400 bp balteum in pshRNA1-3 after cut by SalI, which was identical with the size of the objective gene. Many cells presented green fluorescence after being treated by pshRNA1-4, but there are much more dead green fluorescent cells in the pshRNA1 and pshRNA2 group. hTERT protein and telomerase activity was significantly decreased after treated by pshRNA1 or pshRNA2. It was observed that treatment with pshRNA1 or pshRNA2 in the presence of a valid transfection reagent could reduce cell viability of Hep-2 cells within 96 h (P < 0.01). Under the same culture conditions, cells grew more sparsely and the number of apoptotic cell increased significantly. CONCLUSIONS: shRNA plasmid directed against human telomerase reverse transcriptase can effectively transfect Hep-2 cells. shRNA targeted hTERT gene can significantly inhibit the growth and proliferation of Hep-2 cells, which results in apoptotic cell death. RNA interference may be a promising strategy for the treatment of laryngeal cancer.

Apoptosis↗
PubMed2006

Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial.

BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretroviral therapy with two nucleoside analogue reverse transcriptase inhibitors (didanosine+stavudine) plus either a non-nucleoside reverse transcriptase inhibitor (efavirenz, EFV) or a protease inhibitor (nelfinavir, NFV), or both (EFV/NFV), in patients with HIV-1 infection who had not previously received antiretroviral drugs. Primary outcomes were proportion with undetectable HIV RNA in plasma, and change in CD4 count from baseline at 3 years. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN44582462. FINDINGS: We followed up 911 participants (297 EFV, 311 NFV, 303 EFV/NFV). At 3 years, the proportion with HIV RNA less than 50 copies per mL was highest in the EFV group (188 [74%] EFV, 162 [62%] NFV, 155 [62%] EFV/NFV; p=0.004). Mean (95% CI) increases in CD4 count were 316x10(6) cells per L (288-343) for EFV, 289x10(6) cells per L (262-316) for NFV, and 274x10(6) cells per L (231-291) for EFV/NFV (p=0.1). Fewer participants in the EFV group than in the other groups stopped adequate antiretroviral therapy for more than 30 days (p=0.005). Participants in the EFV/NFV group had shorter time to stopping the initial regimen (p<0.0001) and to a treatment modifying adverse event (p=0.04) than those in the other groups. INTERPRETATION: Starting antiretroviral therapy with a three-drug/two-class regimen including efavirenz was better than starting with regimens including nelfinavir or efavirenz plus nelfinavir in terms of virological suppression and durability of the initial regimen. The shorter time on adequate antiretroviral therapy or to a treatment-modifying adverse event might explain the absence of additional benefit for the four-drug regimen.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Depression of reverse transcriptase activity by hybridoma supernatants: a potential problem in screening for retroviral contamination.

Murine hybridoma cell lines generally produce retroviral particles (type A and/or type C), often in large numbers. We have measured reverse transcriptase activity in the supernatant of some 30 hybridoma lines of murine origin and found that the observed activity expressed as pmoles of [3H]-dGMP incorporated into an acid insoluble polymer, is frequently much lower than would be expected from the amount of retrovirus seen by electron microscopy in the corresponding cells. We demonstrate that this reduction is due to the presence of a nuclease which degrades the high molecular weight product but is not due to a change in the reverse transcriptase activity. This nuclease activity may be associated with mycoplasma contamination of the cell lines.

Animals↗
PubMed1992

3'-Mercapto-2',3'-dideoxynucleotides are high effective terminators of DNA synthesis catalyzed by HIV reverse transcriptase.

Four 3'-mercapto-2',3'-dideoxynucleoside 5'-triphosphates (A, G, C and T) were tested as DNA chain terminator substrates for calf thymus alpha-DNA polymerase, E. coli DNA polymerase I Klenow fragment, terminal deoxynucleotidyl transferase and reverse transcriptases of AMV, HIV and MLV viruses. It was shown that the analogues selectively and irreversibly terminated DNA chain elongation by AMV and HIV reverse transcriptases and the terminal transferase. Other DNA polymerases tested did not use the nucleotide analogues as chain terminator substrate.

Base Sequence↗
PubMed1996

Expression of human immunodeficiency virus type 1 reverse transcriptase in trans during virion release and after infection.

The normal reverse transcription of retroviral RNA is a complex process which depends on the orchestration of several steps throughout the virus life cycle. During the assembly of retroviruses, reverse transcriptase (RT) is directed into the virion as a component of the Gag-Pol polyprotein. In the maturation of the Gag-Pol polyprotein of human immunodeficiency virus type 1 (HIV-1), cleavage by the viral protease occurs during viral budding. After infection, reverse transcription of viral RNA into double-stranded DNA is completed in the cytoplasm of the infected cell. In this study, the processing and reverse transcription of HIV-1 have been examined by separate expression of mature HIV-1 RT and proviral molecules bearing RT mutations. The effects of RT expression in trans during virion release and after viral entry were investigated. Constitutive expression of HIV-1 RT was established in CD4- and non-CD4-expressing cells via the coexpression of its individual subunits, and three HIV-1 RT mutant constructs were generated. The results indicate that a bona fide RT trans complementation does not occur during virion release or after infection. However, after infection of an RT-expressing cell with a high titer RT-defective virus, intracellular reverse transcription can be detected.

Base Sequence↗
PubMed2004

Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells.

Aging is associated with a rise in intracellular reactive oxygen species (ROS) and a loss of telomerase reverse transcriptase activity. Incubation with H2O2 induced the nuclear export of telomerase reverse transcriptase (TERT) into the cytosol in a Src-family kinase-dependent manner. Therefore, we investigated the hypothesis that age-related increase in reactive oxygen species (ROS) may induce the nuclear export of TERT and contribute to endothelial cell senescence. Continuous cultivation of endothelial cells resulted in an increased endogenous formation of ROS starting after 29 population doublings (PDL). This increase was accompanied by mitochondrial DNA damage and preceded the onset of replicative senescence at PDL 37. Along with the enhanced formation of ROS, we detected an export of nuclear TERT protein from the nucleus into the cytoplasm and an activation of the Src-kinase. Moreover, the induction of premature senescence by low concentrations of H2O2 was completely blocked with the Src-family kinase inhibitor PP2, suggesting a crucial role for Src-family kinases in the induction of endothelial cell aging. Incubation with the antioxidant N-acetylcysteine, from PDL 26, reduced the intracellular ROS formation and prevented mitochondrial DNA damage. Likewise, nuclear export of TERT protein, loss in the overall TERT activity, and the onset of replicative senescence were delayed by incubation with N-acetylcysteine. Low doses of the statin, atorvastatin (0.1 micromol/L), had also effects similar to those of N-acetylcysteine. We conclude that both antioxidants and statins can delay the onset of replicative senescence by counteracting the increased ROS production linked to aging of endothelial cells.

Acetylcysteine↗
PubMed1998

The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors.

OBJECTIVE: To investigate the prevalence and magnitude of M184V-mediated changes in susceptibility to zalcitabine, didanosine, stavudine and abacavir (1592U89 succinate) in a cohort of lamivudine-treated patients. DESIGN AND METHODS: A total of 255 samples from patients treated with lamivudine and zidovudine with or without other nucleoside reverse transcriptase inhibitors (NRTI) were analysed for susceptibility to zidovudine, lamivudine, zalcitabine, didanosine and stavudine using a recombinant virus assay. Seventy-three samples originated from patients exposed to zidovudine and lamivudine only. A subset of 27 samples was investigated for cross-resistance to abacavir. Resistance was defined as a change in median inhibitory concentration more than fivefold compared with wild-type (high-level resistance, > 10-fold). A genotypic analysis of plasma-derived reverse transcriptase coding regions was carried out in samples with cross-resistance. RESULTS: The majority of samples displayed wild-type or greater than wild-type sensitivity to zalcitabine, didanosine and stavudine: resistance was seen in 17.2, 9 and 6.3% of the total sample population, respectively. Of these, 1.2, 2.7 and 2.4%, respectively, showed high-level resistance. The prevalence of resistance to a particular NRTI was lower in samples from patients not pretreated with that NRTI and in samples from patients exposed to zidovudine-lamivudine only. Cross-resistance was more prevalent in samples with high ZDV resistance. There was no obvious correlation between cross-resistance and genotype; all but two samples were mutant at codon 184. There were no consistent changes at positions associated with zidovudine resistance. The majority of samples from a subset (n=27) were four- to eightfold less sensitive to abacavir. There were no other genotypic changes in addition to M184V known to be associated with abacavir resistance. CONCLUSIONS: Cross-resistance was not commonly observed in this lamivudine-treated cohort. M184V per se is not expected to compromise subsequent treatment with NRTI such as didanosine-stavudine or combinations containing abacavir.

Anti-HIV Agents↗
PubMed1996

New hydrolyzable tannins, shephagenins A and B, from Shepherdia argentea as HIV-1 reverse transcriptase inhibitors.

Two new hydrolyzable tannins, shephagenins A and B, were isolated along with hippophaenin A and strictinin from the leaf extract of Shepherdia argentea, which showed a remarkable inhibitory activity against human immunodeficiency virus (HIV)-1 reverse transcriptase. Their structures, having a gluconic acid core, have been elucidated on the basis of spectroscopic and chemical methods. The inhibitory effect of the leaf extract on HIV-1 reverse transcriptase was found to be due to tannins, and their activities were stronger than that of (-)-epigallocatechin gallate as a positive control.

Antiviral Agents↗
PubMed2005

Evaluation of a low cost reverse transcriptase assay for plasma HIV-1 viral load monitoring.

We evaluated a low cost manual reverse transcriptase assay (ExaVir Load V.1 and V.2; Cavidi Tech AB) against commercially available HIV RNA assays that quantify viral load to assess its suitability for use in resource-constrained settings. Frozen plasma samples previously tested for RNA by RT-PCR (Roche Diagnostics) and bDNA (Bayer Diagnostics) were retested for RT activity. Text sequence obtained from HIV genotype analysis was submitted to the Stanford HIV Resistance Database V.3.9 and were examined for resistant virus. Detectable RT was present in 98% of samples (V.1; n=127) and in 95% of samples (V.2; n=69) with RNA >10,000 and >1,000 copies/ml respectively. Positive association was found between the log10 RNA copies/ml and log10 RT copies/ml equivalents variables using Pearson's correlation (V.1: r=0.89, n=189; V.2: r=0.89, n=85). The RT activity over time closely followed the trend for RNA levels in samples from 10 HIV seropositive patients with progressive disease. A strong association between RT and RNA was also found with paired samples from 19 patients taken at initiation or change of antiretroviral therapy and again within 2 months. Current (n=40) or no (n=119) exposure to efavirenz therapy had no effect on RT assay performance despite efavirenz binding tightly to the RT enzyme. Samples that demonstrated resistance to the non-nucleoside RT inhibitors (n=112) had a decrease in RT of 0.20 log10 indicating a possible decrease in RT fitness. The RT assay showed good association with current molecular assays, and V.2 is sufficiently sensitive for monitoring HIV viral load in resource-constrained settings.

Alkynes↗