Field-evolved resistance to chlorantraniliprole in the tomato pinworm Tuta absoluta: inheritance, cross-resistance profile, and metabolism

2018 ◽  
Vol 92 (4) ◽  
pp. 1421-1431 ◽  
Author(s):  
Jefferson E. Silva ◽  
Lílian Maria da S. Ribeiro ◽  
Natalia Vinasco ◽  
Raul Narciso C. Guedes ◽  
Herbert Álvaro A. Siqueira
Keyword(s):  
Tuta Absoluta ◽  
Cross Resistance ◽  
Resistance Profile ◽  
Tomato Pinworm

scholarly journals In Vitro Antiviral Activity and Cross-Resistance Profile of PL-100, a Novel Protease Inhibitor of Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 51 (11) ◽  
pp. 4036-4043 ◽  
Author(s):  
Serge Dandache ◽  
Guy Sévigny ◽  
Jocelyn Yelle ◽  
Brent R. Stranix ◽  
Neil Parkin ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Highly Active Antiretroviral Therapy ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Resistance Profile ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Despite the success of highly active antiretroviral therapy, the current emergence and spread of drug-resistant variants of human immunodeficiency virus (HIV) stress the need for new inhibitors with distinct properties. We designed, produced, and screened a library of compounds based on an original l-lysine scaffold for their potentials as HIV type 1 (HIV-1) protease inhibitors (PI). One candidate compound, PL-100, emerged as a specific and noncytotoxic PI that exhibited potent inhibition of HIV-1 protease and viral replication in vitro (Ki , ∼36 pM, and 50% effective concentration [EC50], ∼16 nM, respectively). To confirm that PL-100 possessed a favorable resistance profile, we performed a cross-resistance study using a panel of 63 viral strains from PI-experienced patients selected for the presence of primary PI mutations known to confer resistance to multiple PIs now in clinical use. The results showed that PL-100 retained excellent antiviral activity against almost all of these PI-resistant viruses and that its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir. In almost every case, the increase in the EC50 for PL-100 observed with viruses containing multiple mutations in protease was far less than that obtained with the other drugs tested. These data underscore the potential for PL-100 to be used in the treatment of drug-resistant HIV disease and argue for its further development.

scholarly journals Activities of Atazanavir (BMS-232632) against a Large Panel of Human Immunodeficiency Virus Type 1 Clinical Isolates Resistant to One or More Approved Protease Inhibitors

2003 ◽  
Vol 47 (4) ◽  
pp. 1324-1333 ◽  
Author(s):  
Richard J. Colonno ◽  
Alexandra Thiry ◽  
Kay Limoli ◽  
Neil Parkin
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
The Other ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Resistance Profile ◽  
Immunodeficiency Virus

ABSTRACT To evaluate the cross-resistance profile of the human immunodeficiency virus type 1 protease inhibitor (PI) atazanavir (BMS-232632), a panel of 551 clinical isolates exhibiting a wide array of PI resistance profiles and a variety of genotypic patterns were assayed for susceptibility to atazanavir and six other PIs: amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir. In general, reductions in atazanavir susceptibility in vitro required several amino acid changes and were relatively modest in degree, and susceptibility was retained among isolates resistant to one or two of the currently approved PIs. There was a clear trend toward loss of susceptibility to atazanavir, as isolates exhibited increasing levels of cross-resistance to multiple PIs. Atazanavir appeared to have a distinct resistance profile relative to each of the other six PIs tested based on susceptibility comparisons against this panel of resistant isolates. Analysis of the genotypic profiles of 943 PI-susceptible and -resistant clinical isolates identified a strong correlation between the presence of amino acid changes at specific residues (10I/V/F, 20R/M/I, 24I, 33I/F/V, 36I/L/V, 46I/L, 48V, 54V/L, 63P, 71V/T/I, 73C/S/T/A, 82A/F/S/T, 84V, and 90M) and decreased susceptibility to atazanavir. While no single substitution or combination of substitutions was predictive of atazanavir resistance (change, >3.0-fold), the presence of at least five of these substitutions correlated strongly with loss of atazanavir susceptibility. Mutations associated with reduced susceptibility to each of the other six PIs were also determined.

First report and distribution of the South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) in Togo

2020 ◽  
Author(s):  
Kokou Rodrigue Fiaboe ◽  
Komi Agboka ◽  
Lakpo Koku Agboyi ◽  
Djima Koffi ◽  
Rapheal Ofoe ◽  
...  
Keyword(s):  
Tuta Absoluta ◽  
South American ◽  
The South ◽  
First Report ◽  
South American Tomato Pinworm ◽  
Tomato Pinworm

scholarly journals Thermal plasticity in the invasive south American tomato pinworm Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)

2020 ◽  
Vol 90 ◽  
pp. 102598 ◽  
Author(s):  
Vimbai L. Tarusikirwa ◽  
Reyard Mutamiswa ◽  
Sinead English ◽  
Frank Chidawanyika ◽  
Casper Nyamukondiwa
Keyword(s):  
Tuta Absoluta ◽  
South American ◽  
Thermal Plasticity ◽  
South American Tomato Pinworm ◽  
Tomato Pinworm

scholarly journals In VitroCross-Resistance Profile of Nucleoside Reverse Transcriptase Inhibitor (NRTI) BMS-986001 against Known NRTI Resistance Mutations

2013 ◽  
Vol 57 (11) ◽  
pp. 5500-5508 ◽  
Author(s):  
Zhufang Li ◽  
Brian Terry ◽  
William Olds ◽  
Tricia Protack ◽  
Carol Deminie ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Transcriptase Inhibitor ◽  
Fold Change ◽  
Site Directed Mutagenesis ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Wild Type ◽  
Resistance Profile ◽  
Reverse Transcriptase Inhibitor

ABSTRACTBMS-986001 is a novel HIV nucleoside reverse transcriptase inhibitor (NRTI). To date, little is known about its resistance profile. In order to examine the cross-resistance profile of BMS-986001 to NRTI mutations, a replicating virus system was used to examine specific amino acid mutations known to confer resistance to various NRTIs. In addition, reverse transcriptases from 19 clinical isolates with various NRTI mutations were examined in the Monogram PhenoSense HIV assay. In the site-directed mutagenesis studies, a virus containing a K65R substitution exhibited a 0.4-fold change in 50% effective concentration (EC50) versus the wild type, while the majority of viruses with the Q151M constellation (without M184V) exhibited changes in EC50versus wild type of 0.23- to 0.48-fold. Susceptibility to BMS-986001 was also maintained in an L74V-containing virus (0.7-fold change), while an M184V-only-containing virus induced a 2- to 3-fold decrease in susceptibility. Increasing numbers of thymidine analog mutation pattern 1 (TAM-1) pathway mutations correlated with decreases in susceptibility to BMS-986001, while viruses with TAM-2 pathway mutations exhibited a 5- to 8-fold decrease in susceptibility, regardless of the number of TAMs. A 22-fold decrease in susceptibility to BMS-986001 was observed in a site-directed mutant containing the T69 insertion complex. Common non-NRTI (NNRTI) mutations had little impact on susceptibility to BMS-986001. The results from the site-directed mutants correlated well with the more complicated genotypes found in NRTI-resistant clinical isolates. Data from clinical studies are needed to determine the clinically relevant resistance cutoff values for BMS-986001.

scholarly journals Cross-Resistance Profile Determination of Two Second-Generation HIV-1 Integrase Inhibitors Using a Panel of Recombinant Viruses Derived from Raltegravir-Treated Clinical Isolates

2010 ◽  
Vol 55 (1) ◽  
pp. 321-325 ◽  
Author(s):  
L. Van Wesenbeeck ◽  
E. Rondelez ◽  
M. Feyaerts ◽  
A. Verheyen ◽  
K. Van der Borght ◽  
...  
Keyword(s):  
Second Generation ◽  
Treated Patient ◽  
Integrase Inhibitor ◽  
Cross Resistance ◽  
Integrase Inhibitors ◽  
Genetic Barrier ◽  
Resistance Profile ◽  
Recombinant Viruses ◽  
Treatment Naïve ◽  
Hiv 1

ABSTRACTThe integrase inhibitor raltegravir (RAL) is currently used for the treatment of both treatment-naïve and treatment-experienced HIV-1-infected patients. Elvitegravir (EVG) is in late phases of clinical development. Since significant cross-resistance between RAL and EVG is observed, there is a need for second-generation integrase inhibitors (INIs) with a higher genetic barrier and limited cross-resistance to RAL/EVG. A panel of HIV-1 integrase recombinants, derived from plasma samples from raltegravir-treated patients (baseline and follow-up samples), were used to study the cross-resistance profile of two second-generation integrase inhibitors, MK-2048 and compound G. Samples with Q148H/R mutations had elevated fold change values with all compounds tested. Although samples with the Y143R/C mutation had reduced susceptibility to RAL, they remained susceptible to MK-2048 and compound G. Samples with the N155H mutation had no reduced susceptibility to compound G. In conclusion, our results allowed ranking of the INIs on the basis of the antiviral activities using recombinant virus stocks from RAL-treated patient viruses. The order according to decreasing susceptibility is compound G, MK-2048, and EVG.

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