Abstract:
:Human cytomegalovirus (HCMV) infections cause congenital birth defects and disease in immunosuppressed individuals. Antiviral compounds can control infection yet their use is restricted due to concerns of toxicity and the emergence of drug resistant strains. We have evaluated the impact of an RNA Polymerase I (Pol I) inhibitor, CX-5461 on HCMV replication. CX-5461 inhibits Pol I-mediated ribosomal DNA transcription by binding G-quadruplex DNA structures and also activates cellular stress response pathways. The addition of CX-5461 at both early and late stages of the HCMV infection inhibited viral DNA synthesis and virus production. Interestingly, adding CX-5461 after the onset of viral DNA synthesis resulted in a greater reduction compared to continuous treatment starting early during infection. We observed an accompanying increase in cyclin-dependent kinase inhibitor p21 in infected cells treated late but not early which likely explains the differences. Our previous studies demonstrated the importance of p21 in the antiviral activity of the HCMV kinase inhibitor, maribavir. Addition of CX-5461 increased the anti-HCMV activity of maribavir. Our data demonstrate that CX-5461 inhibits HCMV replication and synergizes with maribavir to disrupt infection.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Westdorp KN,Terhune SSdoi
10.1016/j.antiviral.2018.02.014subject
Has Abstractpub_date
2018-05-01 00:00:00pages
33-38eissn
0166-3542issn
1872-9096pii
S0166-3542(17)30547-8journal_volume
153pub_type
杂志文章abstract::The flavivirus nonstructural 4B protein (NS4B) has recently emerged as a valid antiviral target for drug discovery. Here we review (i) the current understanding of the structure and function of DENV NS4B, (ii) the approaches that have been taken to identify NS4B inhibitors, and (iii) the known inhibitors of flavivirus...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2015.03.007
更新日期:2015-06-01 00:00:00
abstract::A screening for inhibitors of human immunodeficiency virus type 1 (HIV-1) among various types of isopolyoxomolybdates and heteropolyoxomolybdates was carried out by using an in vitro assay system measuring the cytopathogenicity of HIV-1 in CD4+ human MT-4 cells. A novel heteropolyoxomolybdate named PM-104 with the che...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(93)90075-t
更新日期:1993-04-01 00:00:00
abstract::The influenza A (H1N1) virus is a highly contagious acute respiratory disease affecting pigs and humans. This disease causes severe economic loss in many countries, and developing mucosal vaccines is an efficient strategy to control the influenza virus. The neonatal Fc receptor (FcRn) plays an important role in transf...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.11.025
更新日期:2017-02-01 00:00:00
abstract::Infectious bursal disease (IBD) leads to considerable economic losses for the poultry industry by inducing severe immunosuppression and high mortality in chickens. The objective of this study was to determine if RNA interference (RNAi) could be utilized to inhibit IBDV replication in vitro. We selected 3 short interfe...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2007.11.007
更新日期:2008-08-01 00:00:00
abstract::Influenza viruses are major respiratory pathogens responsible for both seasonal epidemics and occasional pandemics worldwide. The current available treatment options have limited efficacy and thus the development of new antivirals is highly needed. We previously reported the identification of a series of cycloheptathi...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2019.03.003
更新日期:2019-05-01 00:00:00
abstract::Filoviruses, which include Ebola virus (EBOV) and Marburg virus, are negative-sense RNA viruses associated with sporadic outbreaks of severe viral hemorrhagic fever characterized by uncontrolled virus replication. The extreme virulence and emerging nature of these zoonotic pathogens make them a significant threat to h...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2018.12.006
更新日期:2019-02-01 00:00:00
abstract::Despite the importance of Dengue virus (DENV) infection in human health, there is not a fully effective vaccine or antiviral treatment against the infection. Since lipids such as cholesterol are required during DENV infection, its uptake and synthesis are increased in infected cells. Ezetimibe is an FDA-approved drug ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2018.10.024
更新日期:2018-12-01 00:00:00
abstract::Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(94)90041-8
更新日期:1994-02-01 00:00:00
abstract::A new adamantane derivative N,N'-bis (ethylene)P(1-adamantyl)-phosphonis diamide, was found to inhibit Rous sarcoma virus replication in much the same manner as reported for the parent compound, 1-adamantanamine hydrochloride. ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(81)90017-6
更新日期:1981-11-01 00:00:00
abstract::The chemically modified DNA, apurinic acid (APA), is cytotoxic for human lymphocytes at concentrations above 100 micrograms/ml. At low concentrations (0.05-1 micrograms/ml) APA acts as an inducer interferon gamma (IFN-gamma) in lymphocytes in vitro; the maximum interferon titer of 50 units/ml was reached at 0.4 microg...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(88)90003-4
更新日期:1988-04-01 00:00:00
abstract::Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.04.003
更新日期:2016-07-01 00:00:00
abstract::Japanese encephalitis virus (JEV) infection is a major cause of acute viral encephalitis both in humans and animals. The domain III of virus envelope protein (EDIII) plays important roles in interacting with host cell receptors to facilitate virus entry. In this study, recombinant JEV EDIII was expressed and purified....
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2012.03.002
更新日期:2012-05-01 00:00:00
abstract::We have shown previously that prostratin, a non-tumor promoting phorbol ester, inhibits chikungunya virus (CHIKV)-induced cytopathic effects in vitro. Prostratin is a potent activator of protein kinases C (PKC), a family of related serine/threonine kinases that regulate many cellular processes such as proliferation an...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.12.020
更新日期:2017-03-01 00:00:00
abstract::The immune evasion of wild-type (wt) rabies virus (RABV) has been attributed to its glycoprotein (G), particularly to their inefficiency to bind/enter into dendritic cells (DCs). However, the domain responsible for G-mediated DC activation is not clear. In the present study, attempts were made to map the domain(s) on ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2017.01.022
更新日期:2017-05-01 00:00:00
abstract::Favipiravir (T-705) is a new anti-influenza drug approved for human use in Japan and progressing through Phase 3 clinical trials in the U.S. In addition to its potent inhibitory effects against influenza virus infection, the compound has been shown to be broadly active against RNA viruses from 9 different families, in...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2015.07.003
更新日期:2015-09-01 00:00:00
abstract::The effect of interferon on the replication of herpes simplex virus types 1 and 2 was studied in two murine macrophage-like cell lines which differ in their ability to synthesize interferon. Higher titers of herpes simplex virus type 1 occurred in PU5-1.8 cell cultures where interferon was not produced than in J774A.1...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(86)90010-0
更新日期:1986-05-01 00:00:00
abstract::The human pathogen hepatitis C virus (HCV) is associated with chronic liver disease. The recent development of the cell culture infectious HCV (HCVcc) system has opened up avenues for detailed studies on the life cycle of the virus and its interaction with the host cell. Current methods to quantitate virus infectivity...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2009.04.007
更新日期:2009-08-01 00:00:00
abstract::The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2019.104667
更新日期:2020-01-01 00:00:00
abstract::Interferon alpha-2b (IFN) alone or in combination with Ribavirin is approved in the United States for the treatment of chronic hepatitis C virus (HCV) infection. We have previously reported that the glucosidase inhibitor, n-butyl deoxynojirimycin (nB-DNJ) inhibits the production of infectious bovine diarrhea virus (BV...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(02)00075-x
更新日期:2002-09-01 00:00:00
abstract::Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replicati...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2020.104749
更新日期:2020-04-01 00:00:00
abstract::Distamycin-A hydrochloride, a synthetic antibiotic, and 2,3-dihydroxy-6-bromo-pyrazino (2,3-beta) pyrazine derivative, were used against tomato spotted wilt virus (TSWV) in tobacco plants. The drugs were applied to the leaves at concentrations of 200 and 400 mg/l. The results showed that both drugs delayed virus sprea...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(83)90032-3
更新日期:1983-08-01 00:00:00
abstract::In 1989, a new type of antibody was identified, first in the sera of dromedaries and later also in all other species of the Camelidae family. These antibodies do not contain a light chain and also lack the first constant heavy domain. Today it is still unclear what the evolutionary advantage of such heavy chain-only a...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2011.09.002
更新日期:2011-12-01 00:00:00
abstract::Herpes simplex virus (HSV) types 1 and 2 are ubiquitous organisms that cause infections in human populations throughout the world. The clinical manifestations of HSV infections are varied, ranging from asymptomatic disease to life-threatening illness in neonates and immunocompromised hosts. This article will review th...
journal_title:Antiviral research
pub_type: 杂志文章,评审
doi:10.1016/j.antiviral.2003.09.006
更新日期:2004-02-01 00:00:00
abstract::Herpesviruses encode a protease that is essential for virus replication. The protease undergoes cleavage to a processed form during capsid maturation. A recombinant 75 kDa form of the protease from human cytomegalovirus was purified and compared with the recombinant 29 kDa processed form. Modification with an active s...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/s0166-3542(02)00051-7
更新日期:2002-08-01 00:00:00
abstract::Site-directed in vitro mutagenesis was used to create analogs of human interferons (IFNs)-alpha 1 and -alpha 4. Analogs were expressed in vitro using SP6 RNA polymerase and a rabbit reticulocyte lysate cell-free protein synthesis system. Amino acid substitutions for the highly conserved residues at positions 33, 121, ...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/0166-3542(89)90066-1
更新日期:1989-08-01 00:00:00
abstract::The prevention and control of disease caused by seasonal and potential pandemic influenza viruses is currently managed by the use influenza vaccines and antivirals. The adamantanes (amantadine and rimantadine) were the first antivirals licensed for use against influenza A viruses and have been used extensively in some...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2006.08.002
更新日期:2007-02-01 00:00:00
abstract::T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-infl...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2016.05.021
更新日期:2016-08-01 00:00:00
abstract::We have previously reported a new class of dendrimers with tryptophan (Trp) residues on the surface that show dual antiviral activities against HIV and enterovirus EV71. The prototype compound of this family is a derivative of pentaerythritol with 12 peripheral Trp groups and trivalent spacer arms. Here a novel series...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2019.06.006
更新日期:2019-08-01 00:00:00
abstract::The anti-human cytomegalovirus (HCMV) activity of tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone), a derivative from Sasa albo-marginata, was studied in the human embryonic fibroblast cell line MRC-5. In a plaque assay, tricin and ganciclovir (GCV) showed concentration-dependent inhibitory properties from 0.05 to 3....
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2011.06.014
更新日期:2011-09-01 00:00:00
abstract::Transcriptional activation of HIV-1 gene expression is partially controlled by the interaction between viral and cellular transcription factors acting at HIV-1 long terminal repeat (LTR) sequences. HIV-1 subtyping at LTR region and nucleotide LTR variability from clinical samples in 48 subjects carrying different HIV-...
journal_title:Antiviral research
pub_type: 杂志文章
doi:10.1016/j.antiviral.2010.08.007
更新日期:2010-11-01 00:00:00