Abstract:
:Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barré syndrome. There are currently no drugs available to treat ZIKV infection, and accordingly, there is an unmet medical need for the discovery of new therapies. High-throughput drug screening efforts focusing on indirect readouts of cell viability are prone to a higher frequency of false positives in cases where the virus is viable in the cell but the cytopathic effect (CPE) is reduced or delayed. Here, we describe a fast and label-free phenotypic high-content imaging assay to detect cells affected by the virus-induced CPE using automated imaging and analysis. Protection from the CPE correlates with a decrease in viral antigen production, as observed by immunofluorescence. We trained our assay using a collection of nucleoside analogues with activity against ZIKV; the previously reported antiviral activities of 2'-C-methylribonucleosides and ribavirin against the Zika virus in Vero cells were confirmed using our developed method. To validate the ability of our assay to reveal new anti-ZIKV compounds, we profiled a novel library of 24 natural product derivatives and found compound 1 to be an inhibitor of the ZIKV-induced cytopathic effect; the activity of the compound was confirmed in human fetal neural stem cells (NSCs). The described technique can be easily leveraged as a primary screening assay for profiling of the activities of large compound libraries against ZIKV and can be expanded to other ZIKV strains and other cell lines displaying morphological changes upon ZIKV infection.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bernatchez JA,Yang Z,Coste M,Li J,Beck S,Liu Y,Clark AE,Zhu Z,Luna LA,Sohl CD,Purse BW,Li R,Siqueira-Neto JLdoi
10.1128/AAC.00725-18subject
Has Abstractpub_date
2018-09-24 00:00:00issue
10eissn
0066-4804issn
1098-6596pii
AAC.00725-18journal_volume
62pub_type
杂志文章abstract::Methicillin-resistant Staphylococcus aureus (MRSA) has become a significant acute and chronic respiratory pathogen. While vancomycin is effective against MRSA, its relatively poor penetration into lung secretions and dose-limiting renal toxicity make it less effective in the respiratory setting. As inhaled administrat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01776-19
更新日期:2020-02-21 00:00:00
abstract::Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creat...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.15.2.161
更新日期:1979-02-01 00:00:00
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更新日期:1974-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.36.9.2054
更新日期:1992-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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abstract::We developed a multiplex real-time SYBR green-based PCR assay for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2) and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5). We showed that the real-time PCR assay developed had high linearity (R2 ≥ 0.996), sensitivity (low detec...
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pub_type: 杂志文章
doi:10.1128/AAC.02292-19
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abstract::Tigemonam, a new monobactam with excellent activity against gram-negative bacteria, was evaluated for in vivo efficacy and absorption after oral administration to laboratory animals. Tigemonam is absorbed when administered orally to mice and dogs. In a variety of gram-negative systemic infections in mice, orally admin...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1987-02-01 00:00:00
abstract::In response to a published concern about the potency and quality of generic vancomycin products, the United States Food and Drug Administration investigated a small sampling of the vancomycin products available in North America with regard to purity, content, and potency. To facilitate identification of impurities, a ...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2012-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
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更新日期:2014-10-01 00:00:00
abstract::Carbapenemase-producing Enterobacteriaceae isolates (n = 110) from health care centers in central Indiana (from 2010 to 2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline, or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00389-17
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abstract::A multidrug-resistant (MDR) Pseudomonas fulva strain was isolated in 2006 from a urine sample. The isolate harbored the blaIMP-1 gene, which was located in a chromosomal Tn402-like class 3 integron as a gene cassette array of aacA31-fosE-blaIMP-1 Two mutations in gyrA and one mutation in parC were detected in quinolon...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00701-18
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:1977-10-01 00:00:00
abstract::Using the techniques of gap misrepair mutagenesis and site-directed mutagenesis, we have generated two novel quinolone resistance mutations of the Escherichia coli DNA gyrase A protein. DNA sequencing showed these mutations to be Ser-83----Ala and Gln-106----Arg. The mutant proteins were overproduced and purified, and...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1991-02-01 00:00:00
abstract::Vaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, do...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00568-16
更新日期:2016-09-23 00:00:00
abstract::In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic Vibrio cholerae strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing V. cholerae isolates were recovered along the German coastline. These isolates a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02112-18
更新日期:2019-03-27 00:00:00
abstract::The activities of the purine acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) against two human and five animal strains of cytomegalovirus were compared with those of acyclovir. DHPG was significantly more active than acyclovir against all but one (mouse cytomegalovirus) of the strains tested, with 5...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.2.240
更新日期:1985-08-01 00:00:00
abstract::Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.8.1600
更新日期:1990-08-01 00:00:00
abstract::We identified GRL-1388 and -1398, potent nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran (Tp-THF). GRL-1388 was as potent as darunavir (DRV) against various drug-resistant HIV-1 laboratory strains with 50% ef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01540-10
更新日期:2011-04-01 00:00:00
abstract::Monotherapy with isoniazid or amikacin or clarithromycin or combinations of two of these drugs showed nil to modest therapeutic activity in beige mice infected with Mycobacterium avium. However, the combination of all three, isoniazid-amikacin-clarithromycin, markedly reduced CFUs in both spleens and lungs after 91 da...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1998-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2012-01-01 00:00:00
abstract::The lipopeptidic antibiotic daptomycin is reported to reduce experimental tobramycin nephrotoxicity (D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990; C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. C. Gilbert, Antimicrob. Agents C...
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更新日期:1994-04-01 00:00:00
abstract::Pseudomonas aeruginosa infections result in high morbidity and mortality rates for individuals with cystic fibrosis (CF), with premature death often occurring. These infections are complicated by the formation of biofilms in the sputum. Antibiotic therapy is stymied by antibiotic resistance of the biofilm matrix, maki...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02919-15
更新日期:2016-07-22 00:00:00
abstract::The genetic basis for fluoroquinolone resistance was examined in 30 high-level fluoroquinolone-resistant Escherichia coli clinical isolates from Beijing, China. Each strain also demonstrated resistance to a variety of other antibiotics. PCR sequence analysis of the quinolone resistance-determining region of the topois...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.5.1515-1521.2001
更新日期:2001-05-01 00:00:00
abstract::Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3523-3529.2004
更新日期:2004-09-01 00:00:00
abstract::Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plas...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-06-01 00:00:00
abstract::A novel streptogramin A, pleuromutilin, and lincosamide resistance determinant, Vga(E), was identified in porcine methicillin-resistant Staphylococcus aureus (MRSA) ST398. The vga(E) gene encoded a 524-amino-acid protein belonging to the ABC transporter family. It was found on a multidrug resistance-conferring transpo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00528-11
更新日期:2011-10-01 00:00:00
abstract::A novel gene cassette, aacA43, was identified in the aadB-aacA43-oxa10-smr2 cassette array in a class 1 integron. Like related aminoglycoside-(6')-acetyltransferases, AacA43 confers clinically relevant resistance to kanamycin, tobramycin, and some less-used aminoglycosides but not to gentamicin. Although transferable ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01582-10
更新日期:2011-06-01 00:00:00
abstract::Penicillin-binding protein (PBP) 2 is the major PBP of five that have been identified in susceptible strains of Staphylococcus aureus. Beta-lactam antibiotic binding to PBP 2 is important for the antibacterial effect. Antibiotic binding to PBP 2 in strain 209P was examined with sodium dodecyl sulfate-polyacrylamide ge...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.3.656
更新日期:1992-03-01 00:00:00
abstract::The VanR-VanS two-component system is responsible for inducing resistance to glycopeptide antibiotics in various bacteria. We have performed a comparative study of the VanR-VanS systems from two streptomyces strains, Streptomyces coelicolor and Streptomyces toyocaensis, to characterize how the two proteins cooperate t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01367-15
更新日期:2015-12-28 00:00:00