593 research outputs found
SARS-CoV-2 RNA dependent RNA polymerase as a therapeutic target for COVID-19
No full textIntroduction. The current SARS-CoV-2 pandemic urgently demands for both prevention and treatment strategies. RNA-dependent RNA-polymerase (RdRp), which has no counterpart in human cells, is an excellent target for drug development. Given the time-consuming process of drug development, repurposing drugs approved for other indications or at least successfully tested in terms of safety and tolerability, is an attractive strategy to rapidly provide an effective medication for severe COVID-19 cases. Areas covered. The currently available data and upcoming studies on RdRp which can be repurposed to halt SARS-CoV-2 replication, are reviewed. Expert opinion. Drug repurposing and design of novel compounds are proceeding in parallel to provide a quick response and new specific drugs, respectively. Notably, the proofreading SARS-CoV-2 exonuclease activity could limit the potential for drugs designed as immediate chain terminators and favour the development of compounds acting through delayed termination. While vaccination is awaited to curb the SARS-CoV-2 epidemic, even partially effective drugs from repurposing strategies can be of help to treat severe cases of disease. Considering the high conservation of RdRp among coronaviruses, an improved knowledge of its activity in vitro can provide useful information for drug development or drug repurposing to combat SARS-CoV-2 as well as future pandemics
Supplemental_Matherial_Cell_based_Immunodetection_Assay_DENV_ZIKV_Antivirals_by_Vicenti_et_al_rev_2 – Supplemental material for Development of a Cell-Based Immunodetection Assay for Simultaneous Screening of Antiviral Compounds Inhibiting Zika and Dengue Virus Replication
No full textSupplemental material, Supplemental_Matherial_Cell_based_Immunodetection_Assay_DENV_ZIKV_Antivirals_by_Vicenti_et_al_rev_2 for Development of a Cell-Based Immunodetection Assay for Simultaneous Screening of Antiviral Compounds Inhibiting Zika and Dengue Virus Replication by Ilaria Vicenti, Filippo Dragoni, Alessia Giannini, Federica Giammarino, Michele Spinicci, Francesco Saladini, Adele Boccuto and Maurizio Zazzi in SLAS Discovery</p
Rezension zu: Ilaria Bignamini/Clare Hornsby, Digging and Dealing in Eighteenth-Century Rome. With additional research by Irma Della Giovampaola and Jonathan Yarker (New Haven and London 2010)
No full textAgreement between an in-house replication competent and a reference replication defective recombinant virus assay for measuring phenotypic resistance to HIV-1 protease, reverse transcriptase, and integrase inhibitors
No full textBACKGROUND:
Although clinical management of drug resistance is routinely based on genotypic methods, phenotypic assays remain necessary for the characterization of novel HIV-1 inhibitors, particularly against common drug-resistant variants. We describe the development and assessment of the performance of a recombinant virus assay for measuring HIV-1 susceptibility to protease (PR), reverse transcriptase (RT), and integrase (IN) inhibitors.
METHODS:
The system is based on the creation of replication-competent chimeric viruses through homologous recombination between patient or laboratory virus-derived PCR fragments and the corresponding NL4-3 vector where the whole Gag-PR, RT-RNaseH or IN coding regions has been deleted through inverse PCR. The susceptibility to nucleoside (NRTIs) and non-nucleoside (NNRTIs) RT inhibitors and to IN inhibitors (INIs) is calculated through a single-round infection assay in TZM-bl cells, while protease inhibitor (PI) activity is determined through a first round of infection in MT-2 cells followed by infection of TZM-bl cells with MT-2 supernatants.
RESULTS:
The assay showed excellent reproducibility and accuracy when testing PI, NRTI, NNRTI, and INI susceptibility of drug-resistant clones previously characterized through the reference pseudoparticle-based Phenosense assay. The coefficient of interassay variation in fold change (FC) resistance was 12.0%-24.3% when assaying seven drug/clones pairs in three runs. FC values calculated by the Phenosense and in-house for 20 drug/clones pairs were in good agreement, with mean±SD ratio of 1.14±0.33 and no cases differing by more than twofold.
CONCLUSIONS:
The described phenotypic assay can be adopted to evaluate the antiviral activity of licensed and investigational HIV-1 drugs targeting any of the three HIV-1 enzymes
Use of peripheral blood DNA for genotypic antiretroviral resistance testing in drug-naïve HIV-infected subjects.
No full textParallel analysis of peripheral blood mononuclear cell DNA and plasma RNA from 169 drug-naive human immunodeficiency virus-infected subjects revealed that evaluation of both compartments increases the sensitivity of detection of drug resistance-related mutations, compared with examination of either source alone. Peripheral blood mononuclear cell DNA may play a role in the surveillance of transmitted antiretroviral resistance
Data of cost-optimal solutions and retrofit design methods for school renovation in a warm climate
No full textAbstract"Efficient Solutions and Cost-Optimal Analysis for Existing School Buildings" (Paolo Maria Congedo, Delia D’Agostino, Cristina Baglivo, Giuliano Tornese, Ilaria Zacà) [1] is the paper that refers to this article. It reports the data related to the establishment of several variants of energy efficient retrofit measures selected for two existing school buildings located in the Mediterranean area. In compliance with the cost-optimal analysis described in the Energy Performance of Buildings Directive and its guidelines (EU, Directive, EU 244,) [2,3], these data are useful for the integration of renewable energy sources and high performance technical systems for school renovation. The data of cost-efficient high performance solutions are provided in tables that are explained within the following sections.The data focus on the describe school refurbishment sector to which European policies and investments are directed. A methodological approach already used in previous studies about new buildings is followed (Baglivo Cristina, Congedo Paolo Maria, D׳Agostino Delia, Zacà Ilaria, 2015; IlariaZacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo; Baglivo Cristina, Congedo Paolo Maria, D’Agostino Delia, Zacà Ilaria, 2015; Ilaria Zacà, Delia D’Agostino, Paolo Maria Congedo, Cristina Baglivo, 2015; Paolo Maria Congedo, Cristina Baglivo, IlariaZacà, Delia D’Agostino,2015) [4–8]. The files give the cost-optimal solutions for a kindergarten (REF1) and a nursery (REF2) school located in Sanarica and Squinzano (province of Lecce Southern Italy). The two reference buildings differ for construction period, materials and systems.The eleven tables provided contain data about the localization of the buildings, geometrical features and thermal properties of the envelope, as well as the energy efficiency measures related to walls, windows, heating, cooling, dhw and renewables. Output values of energy consumption, gas emission and costs are given for a financial and a macro-economic analysis.This data article provides 288 and 96 combinations for REF1 and REF2, respectively. The output values are obtained using the software ProCasaClima 2015v.2.0
Author Correction: Gluten consumption and inflammation affect the development of celiac disease in at-risk children
No full textThe original version of this Article contained an error in the spelling of the authors Renata Auricchio, Ilaria Calabrese, Martina Galatola, Donatella Cielo, Fortunata Carbone, Marianna Mancuso, Giuseppe Matarese, Riccardo Troncone, Salvatore Auricchio & Luigi Greco which were incorrectly given as Auricchio Renata, Calabrese Ilaria, Galatola Martina, Cielo Donatella, Carbone Fortunata, Mancuso Marianna, Matarese Giuseppe, Troncone Riccardo, Auricchio Salvatore & Greco Luigi. The original article has been corrected
Development of an internally controlled quantitative PCR to measure total cell-associated HIV-1 DNA in blood
No full textComparative analysis of different cell systems for Zika virus (ZIKV) propagation and evaluation of anti-ZIKV compounds in vitro
No full textA strong correlation between Zika virus (ZIKV) infection and severe neurological disease in newborns and occasionally adults has emerged in the Brazilian outbreak. Efficient human cell-based assays are required to test candidate inhibitors of ZIKV replication. The aim of this work was to investigate ZIKV propagation and quantification in different cell lines. The human (U87, A549, Huh7), mosquito (C6/36) and monkey (VERO E6) cell lines tested were all permissive to ZIKV infection. When assessed by plaque forming units (PFU) in three different target cell lines, the maximal production of ZIKV was achieved in Huh7 at day 3 post-infection (6.38 ± 0.44 log10PFU/ml). The C6/36 cell line showed a low and slow production of virus when compared with other cell lines. A549 readout cells generated a larger number of plaques compared to Huh7 but not to VERO E6 cells. ZIKV PFU and RNA titers showed the highest correlation when Huh7 and A549 were used as the producer and readout cells, respectively. Also, U87 cells produced ZIKV RNA titers which were highly correlated with PFU independently from the readout cell line. Using the best virus-cell system, sofosbuvir and ribavirin EC50were 1.2 Î1⁄4M and 1.1 Î1⁄4M when measured through plaque assay, and 4.2 Î1⁄4M and 5.2 Î1⁄4M when measured by quantitative real time PCR (qRT-PCR), respectively. In summary, ZIKV can efficiently infect different human cell lines and rapidly reach peak viral titers. Overall, A549 cells appear to be as efficient as the VERO E6 gold standard for plaque assay allowing the use of human, rather than simian, cells for evaluating candidate anti-ZIKV compounds by the reference assay. The possibility to replace the labor-intensive plaque assay with the more rapid and easy-to-perform qRT-PCR is appealing and warrants further investigation
The HIV-1 integrase E157Q polymorphism per se does not alter susceptibility to raltegravir and dolutegravir in vitro
No full textThe HIV-1 integrase E157Q natural polymorphism has been reported to cause one case of raltegravir (RAL) and dolutegravir (DTG) failure. Six recombinant viruses were constructed containing integrase from clinical HIV-1 isolates found to harbour E157Q as the only integrase strand inhibitor (INSTI) resistance-related mutation. Phenotypic analysis showed that E157Q results in minimal changes in RAL and DTG susceptibility. Together with data retrieved from the Stanford HIV database, our results indicate that E157Q is not a relevant INSTI resistance mutation per se. The previously reported case of E157Q-based resistance must have resulted from combined as yet unidentified integrase polymorphisms
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