Abstract:
:Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintricarboxylic acid (ATA), to examine their effects on viral replication. We found that 6-OHDA inhibited HCV replication; however, 6-OHDA was a less potent inhibitor of RISC than either SUR or ATA. By generating a novel chemical probe (6-OHDA-yne), we determined that 6-OHDA covalently modifies host and virus proteins. Moreover, 6-OHDA was shown to be an alkylating agent that is capable of generating adducts with a number of enzymes involved in the oxidative stress response. Furthermore, modification of viral enzymes with 6-OHDA and 6-OHDA-yne was found to inhibit their enzymatic activity. Our findings suggest that 6-OHDA is a probe for oxidative stress as well as protein alkylation, and these properties together contribute to the antiviral effects of this compound.
journal_name
ACS Infect Disjournal_title
ACS infectious diseasesauthors
Lafreniere MA,Powdrill MH,Singaravelu R,Pezacki JPdoi
10.1021/acsinfecdis.6b00098subject
Has Abstractpub_date
2016-11-11 00:00:00pages
863-871issue
11issn
2373-8227journal_volume
2pub_type
杂志文章abstract::Across zoonotic pathogens, RNA viruses are responsible for disproportionate levels of human disease, suffering, and death. Neurotropic RNA viruses (e.g., rabies, Japanese and Eastern Equine Encephalitis, Ebola, West Nile, Powassan) infect the brain and spinal cord, causing meningitis, encephalitis, microcephaly, and G...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00339
更新日期:2019-12-13 00:00:00
abstract::The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus. ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00030
更新日期:2016-03-11 00:00:00
abstract::Flaviviruses causes significant human disease. Recent outbreaks of the Zika virus highlight the need to develop effective therapies for this class of viruses. Previously we identified niclosamide as a broad-spectrum inhibitor for flaviviruses by targeting the interface between viral protease NS3 and its cofactor NS2B....
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00217
更新日期:2020-10-09 00:00:00
abstract::Amonabactins are a group of four related catecholate siderophores produced by several species of the genus Aeromonas, including A. hydrophila and the fish pathogen A. salmonicida subsp. salmonicida. Although the gene cluster encoding amonabactin biosynthesis also contains a gene that could encode the ferri-siderophore...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00274
更新日期:2019-11-08 00:00:00
abstract::In response to the urgent need for new antibiotic development strategies, antimicrobial peptides and their synthetic mimetics are being investigated as promising alternatives to traditional antibiotics. To facilitate their development into clinically viable candidates, we need to understand what molecular features and...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00079
更新日期:2018-08-10 00:00:00
abstract::Hypervirulent Klebsiella pneumoniae (hvKp) is an underrecognized pathotype of K. pneumoniae since the majority of cases have occurred in East Asia. However, hvKp is a public health threat due to its ability to infect healthy individuals, ongoing dissemination, and acquisition of resistance determinants. hvKp-directed ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00117
更新日期:2019-07-12 00:00:00
abstract::Enterovirus 71 (EV71) is a major etiological agent of hand, foot, and mouth disease, for which there is no antiviral therapy. We have developed densely sulfated disaccharide heparan sulfate (HS) analogues that are potent small molecule inhibitors of EV71 infection, binding to the viral capsid and acting as decoy recep...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00070
更新日期:2019-10-11 00:00:00
abstract::Ebola virus (EBOV), a member of the family Filoviridae, is a nonsegmented negative-sense RNA virus that causes severe, often lethal, disease in humans. EBOV RNA synthesis is carried out by a complex that includes several viral proteins. The function of this machinery is essential for viral gene expression and viral re...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00053
更新日期:2015-08-14 00:00:00
abstract::Glycopeptide antibiotics (GPAs) are a key weapon in the fight against drug resistant bacteria, with vancomycin still a mainstream therapy against serious Gram-positive infections more than 50 years after it was first introduced. New, more potent semisynthetic derivatives that have entered the clinic, such as dalbavanc...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00258
更新日期:2018-05-11 00:00:00
abstract::Enterovirus D68 (EV-D68) is an RNA virus that causes respiratory illnesses mainly in children. In severe cases, it can lead to neurological complications such as acute flaccid myelitis (AFM). EV-D68 belongs to the enterovirus genera of the Picornaviridae family, which also includes many other significant human pathoge...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00120
更新日期:2020-07-10 00:00:00
abstract::Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00106
更新日期:2018-02-09 00:00:00
abstract::Conventional antibiotics are not effective in treating infections caused by drug-resistant or persistent nongrowing bacteria, creating a dire need for the development of new antibiotics. We report that the small molecule nTZDpa, previously characterized as a nonthiazolidinedione peroxisome proliferator-activated recep...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00161
更新日期:2018-11-09 00:00:00
abstract::Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of Staphylococcus aureus SrtA by screening a library of...
journal_title:ACS infectious diseases
pub_type: 信件
doi:10.1021/acsinfecdis.9b00265
更新日期:2020-02-14 00:00:00
abstract::Gram-negative bacteria are intrinsically resistant to many antibiotics. Species that have acquired multidrug resistance and cause infections that are effectively untreatable present a serious threat to public health. The problem is broadly recognized and tackled at both the fundamental and applied levels. This paper s...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00097
更新日期:2015-01-01 00:00:00
abstract::Recent studies on 3,6-diphenylated imidazopyridazines have demonstrated impressive in vitro activity and in vivo efficacy in mouse models of malaria infection. Herein, we report the synthesis and antiplasmodium evaluation of a new series of amidated analogues and demonstrate that these compounds potently inhibit Plasm...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00481
更新日期:2021-01-08 00:00:00
abstract::Emerging β-lactamase-mediated resistance is threatening the clinical utility of the single most prominent class of antibacterial agents used in medicine, the β-lactams. The diazabicyclooctane avibactam is able to inhibit a wider range of serine β-lactamases than has been previously observed with β-lactamase inhibitors...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00007
更新日期:2015-04-10 00:00:00
abstract::In the field of Parkinson's disease (PD) research, leucine-rich repeat kinase 2 (LRRK2) remains one of the most enigmatic kinases. LRRK2 pathogenic mutations result in increased kinase activity, making LRRK2 an attractive therapeutic target for PD. For over 10 years, the identification of a bona fide substrate and a p...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00051
更新日期:2019-06-14 00:00:00
abstract::Bacterial quorum sensing (QS) is being contemplated as a promising target for developing innovative diagnostic and therapeutic strategies. Here we report for the first time the development of antibodies against 2-heptyl-4-quinolone (HHQ), a signaling molecule from the pqs QS system of Pseudomonas aeruginosa, involved ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00604
更新日期:2020-12-11 00:00:00
abstract::The fusion between the viral and the target cell membrane is a crucial step in the life cycle of enveloped viruses. The blocking of this process is a well-known therapeutic approach that led to the development of the fusion inhibitor peptide enfuvirtide, clinically used against human immunodeficiency virus (HIV) type ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00321
更新日期:2019-04-12 00:00:00
abstract::A series of derivatives of the 4,5-disubstituted class of 2-deoxystreptamine aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin was prepared and assayed for (i) their ability to inhibit protein synthesis by bacterial ribosomes and by engineered bacterial ribosomes carrying eukaryotic decoding A sites, ...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.9b00128
更新日期:2019-10-11 00:00:00
abstract::Human African trypanosomiasis (HAT) is a fatal infectious disease caused by the eukaryotic pathogen Trypanosoma brucei (Tb). Available treatments are difficult to administer and have significant safety issues. S-Adenosylmethionine decarboxylase (AdoMetDC) is an essential enzyme in the parasite polyamine biosynthetic p...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00022
更新日期:2017-07-14 00:00:00
abstract::Computer-aided screening of antimicrobial peptides (AMPs) is a promising approach for discovering novel therapies against multidrug-resistant bacterial infections. Here, we functionally and structurally characterized an Escherichia coli-derived AMP (EcDBS1R5) previously designed through pattern identification [α-helic...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00219
更新日期:2018-12-14 00:00:00
abstract::Glycosylated proteins (i.e., mucins, IgG) are important mediators of innate antiviral immunity in the vagina; however, our current knowledge of the role that glycan themselves play in genital immunity is relatively low. Herein, we evaluate the relationship between innate antiviral immunity and glycomic composition in ...
journal_title:ACS infectious diseases
pub_type: 杂志文章,随机对照试验
doi:10.1021/acsinfecdis.8b00157
更新日期:2018-11-09 00:00:00
abstract::Balhimycin, a vancomycin-type glycopeptide, is a lipid II targeting antibiotic produced by Amycolatopsis balhimycina. A. balhimycina has developed a self-resistance mechanism based on the synergistic action of different enzymes resulting in modified peptidoglycan. The canonical resistance mechanism against glycopeptid...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00011
更新日期:2015-06-12 00:00:00
abstract::Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillb...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.7b00064
更新日期:2017-08-11 00:00:00
abstract::Multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis are resistant to first- and second-line drug regimens and resulted in 210,000 fatalities in 2013. In the current study, we screened a library of aquatic bacterial natural product fractions for their ability to inhibit this pathogen. A frac...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.5b00005
更新日期:2015-04-10 00:00:00
abstract::Evolving antimicrobial resistance has motivated the search for novel targets and alternative therapies. Caseinolytic protease (ClpP) has emerged as an enticing new target since its function is conserved and essential for bacterial fitness, and because its inhibition or dysregulation leads to bacterial cell death. ClpP...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.0c00599
更新日期:2020-12-11 00:00:00
abstract::Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (M...
journal_title:ACS infectious diseases
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acsinfecdis.0c00291
更新日期:2020-07-10 00:00:00
abstract::To explore the possibility of constrained peptides to target Plasmodium-infected cells, we designed a J domain mimetic derived from Plasmodium falciparum calcium-dependent protein kinase 1 ( PfCDPK1) as a strategy to disrupt J domain binding and inhibit PfCDPK1 activity. The J domain disruptor (JDD) peptide was confor...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.8b00347
更新日期:2019-04-12 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic approved for use against Gram-positive organisms, including highly resistant species. A number of studies have suggested that daptomycin kills bacteria by membrane permeabilization and depolarization. Recently a model membrane system consisting of 1,2-dimyristoyl-sn-glycero-3-pho...
journal_title:ACS infectious diseases
pub_type: 杂志文章
doi:10.1021/acsinfecdis.6b00152
更新日期:2016-10-14 00:00:00