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 cycloheptathiophene-3-carboxamide compounds as influenza A virus inhibitors that act by targeting the protein-protein interactions between the PA-PB1 subunits of the viral polymerase. In this study, we characterized the antiviral properties of the most promising compounds as well as investigated their propensity to induce drug resistance. Our results show that some of the selected compounds possess potent, broad-spectrum anti-influenza activity as they efficiently inhibited the replication of several strains of influenza A and B viruses, including an oseltamivir-resistant clinical isolate, with nanomolar or low-micromolar potency. The most promising compounds specifically inhibited the PA-PB1 binding in vitro and interfered with the influenza A virus polymerase activity in a cellular context, without showing cytotoxicity. The most active PA-PB1 inhibitors showed to possess a drug resistance barrier higher than that of oseltamivir. Indeed, no viral variants with reduced susceptibility to the selected compounds emerged after serial passages of influenza A virus under drug selective pressure. Overall, our studies identified potent PA-PB1 inhibitors as promising candidates for the development of new anti-influenza drugs.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Nannetti G,Massari S,Mercorelli B,Bertagnin C,Desantis J,Palù G,Tabarrini O,Loregian Adoi
10.1016/j.antiviral.2019.03.003subject
Has Abstractpub_date
2019-05-01 00:00:00pages
55-64eissn
0166-3542issn
1872-9096pii
S0166-3542(18)30659-4journal_volume
165pub_type
杂志文章abstract：BACKGROUND:Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clini...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2013.05.013
更新日期：2013-08-01 00:00:00
abstract：:The biological evaluation of mononucleotide prodrugs (pronucleotides) of various nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine (AZT), zalcitabine (ddC) and lamivudine (3TC) was reported in human T-lymphoid MOLT-4/8 cells which were grown continuously for more than 1 year in a medium containing...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(01)00205-4
更新日期：2002-02-01 00:00:00
abstract：:Laninamivir, a potent neuraminidase (NA) inhibitor, is an active metabolite of laninamivir octanoate (code name: CS-8958) which is a long acting NA inhibitor and is commercially available under the brand name Inavir in Japan to complete the treatment of influenza by a single inhalation. It is supposed that the long ac...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2013.08.004
更新日期：2013-10-01 00:00:00
abstract：:Vaccination against smallpox may result in a variety of complications, ranging in severity from benign to lethal. Universal vaccination was halted in the US in 1972, so almost half the present population has never been vaccinated. Because side effects occur most often in first-time vaccinees, current plans for rapid l...
journal_title：Antiviral research
pub_type： 杂志文章,评审
doi：10.1016/s0166-3542(03)00008-1
更新日期：2003-04-01 00:00:00
abstract：:In the event of a bioterror attack with variola virus (smallpox), exposure may only be identified following onset of fever. To determine if antiviral therapy with brincidofovir (BCV; CMX001) initiated at, or following, onset of fever could prevent severe illness and death, a lethal rabbitpox model was used. BCV is in ...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2017.04.002
更新日期：2017-07-01 00:00:00
abstract：:Prunellin, an anti-HIV active compound, was isolated from aqueous extracts of the Chinese medicinal herb, Prunella vulgaris, and purified to chromatographic homogeneity. Infrared and NMR spectroscopy identified prunellin as a polysaccharide. Elemental analyses, precipitation with calcium(II), barium(II), or 9-aminoacr...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/0166-3542(89)90036-3
更新日期：1989-06-01 00:00:00
abstract：:Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world and can lead to a life-threatening disease. We therefore developed an animal model to evaluate candidate anti-CMV drugs and to further define the pathogenesis of CMV infections. Newborn guinea pigs were infected by intraperit...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(03)00151-7
更新日期：2003-09-01 00:00:00
abstract：:Amantadine and rimantadine hydrochloride were tested for stability after storage at different temperatures and under different conditions for extended periods of time. Both compounds were quite stable after storage for at least 25 years at ambient temperature; they both retained full antiviral activity after long-term...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(98)00015-1
更新日期：1998-06-01 00:00:00
abstract：:The reverse transcriptase (RT) of HIV which has been inhibited by the incorporation of AZT into the primer strand is subject to a deblocking reaction by cellular ATP. This reaction yields unblocked primer plus the dinucleoside tetraphosphate, AZTp(4)A. In the present study, we report that AZTp(4)A is an excellent subs...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(03)00003-2
更新日期：2003-05-01 00:00:00
abstract：:Despite an urgent medical need, a broadly effective anti-viral therapy for the treatment of infections with hepatitis C viruses (HCVs) has yet to be developed. One of the approaches to anti-HCV drug discovery is the design and development of specific small molecule drugs to inhibit the proteolytic processing of the HC...
journal_title：Antiviral research
pub_type： 杂志文章,评审
doi：
更新日期：1999-02-01 00:00:00
abstract：:In spite of a decrease in the prevalence and incidence seen in recent years, chronic hepatitis B (CHB) still remains a major healthcare challenge, prevalent mostly in developing but also in developed regions. CHB is associated with significant morbidity and mortality, secondary to the complications of disease progress...
journal_title：Antiviral research
pub_type： 杂志文章,评审
doi：10.1016/j.antiviral.2020.104783
更新日期：2020-05-01 00:00:00
abstract：:Oxymatrine (OMTR) is an anti-hepatitis drug used in China. Its mechanism of action is unknown. Recently, we found that OMTR inhibits hepatitis B virus (HBV) via down-regulating the expression of heat-stress cognate 70 (Hsc70), a host protein required for HBV DNA replication. Goal of this study was to assess the effect...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2011.01.005
更新日期：2011-03-01 00:00:00
abstract：:The bovine immunodeficiency virus (BIV) and human immunodeficiency virus types 1 and 2 (HIV-1 and -2) are members of the lentivirus genus of retroviruses. Although DNA sequences of these viruses have diverged considerably, the BIV genome organization, function of structural and regulatory genes, and replication cycle ...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(96)00990-4
更新日期：1996-12-01 00:00:00
abstract：:Nalidixic acid and oxolinic acid, two antibacterial agents known to inhibit bacterial DNA gyrase, are shown to suppress the replication, as well as the cytopathic effect, of BK virus in Vero cell cultures. The inhibition of virus replication was detectable at day 4 post infection in cultures which had been continuousl...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/0166-3542(88)90004-6
更新日期：1988-04-01 00:00:00
abstract：:Amino acid 1092 (AA1092) in capsid protein 1 of coxsackievirus B3 (CVB3) is located in close vicinity to the central phenoxy group of capsid binders (i.e. pleconaril). Whereas isoleucine is associated with drug susceptibility, leucine and methionine confer resistance to pleconaril. In the present study, novel analogue...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2008.09.002
更新日期：2009-01-01 00:00:00
abstract：:Nucleoside analogues have been the most successful antiviral compounds. Likewise, they are the most intriguing antiviral compounds, because of their structural relationship to natural nucleosides. This is also the reason why the design process of a potential selective antiviral nucleoside is so difficult. Too many nat...
journal_title：Antiviral research
pub_type： 杂志文章,评审
doi：10.1016/j.antiviral.2006.04.004
更新日期：2006-09-01 00:00:00
abstract：:We have investigated the inhibitory effect of trans-cinnamaldehyde (CA), one of the principal constituents of essential oil derived from Cinnamomi cortex, on the growth of influenza A/PR/8 virus in vitro and in vivo. When 1-h drug treatment was initiated at various times post-infection (p.i.) in Madin-Darby canine kid...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2007.01.003
更新日期：2007-04-01 00:00:00
abstract：:Human cytomegalovirus infection can lead to life-threatening clinical manifestations particularly in the immunocompromised host. Current therapy options face severe limitations leading to a continued search for alternative drug candidates. Viral replication is dependent on a balanced interaction between viral and cell...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2013.04.017
更新日期：2013-08-01 00:00:00
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journal_title：Antiviral research
pub_type： 杂志文章,meta分析
doi：10.1016/j.antiviral.2010.12.003
更新日期：2011-02-01 00:00:00
abstract：:Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts. Subjects were randomized to receive subcutaneous injections of either 2 x 10(6) or 4 x 10(6) IU/m2 of IFN-beta (Biogen) three time...
journal_title：Antiviral research
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1016/s0166-3542(97)01037-1
更新日期：1997-06-01 00:00:00
abstract：:Previously, we found that a ganciclovir (GCV)-resistant clinical human cytomegalovirus (HCMV) isolate had an amino acid substitution at codon 501 (Leu --> Phe) in the delta-region C of the DNA polymerase gene. DNA polymerases have now been (partially) purified from both the GCV-resistant and sensitive parental strains...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/s0166-3542(00)00063-2
更新日期：2000-02-01 00:00:00
abstract：:HIV-associated neurocognitive disorders (HAND) remain prevalent even with widespread use of combination antiretroviral therapy (ART), suggesting a potential role for co-morbidities in neurologic decline. Indeed, it is well established that ART drugs, particularly HIV protease inhibitors, can induce hyperlipidemia, lip...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2012.04.010
更新日期：2012-07-01 00:00:00
abstract：:Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne virus found in tropical regions of Africa and South America that causes severe hepatic disease and death in humans. Despite the availability of effective vaccines, YFV is responsible for an estimated 200,000 cases and 30,000 deaths annuall...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2012.02.001
更新日期：2012-04-01 00:00:00
abstract：:Herpes simplex virus-1 (HSV-1) infection is known to cause skin blisters, keratitis as well as deadly cases of encephalitis in some situations. Only a few therapeutic modalities are available for this globally prevalent infection. Very recently, a small molecule BX795 was identified as an inhibitor of HSV-1 protein sy...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2020.104814
更新日期：2020-08-01 00:00:00
abstract：:Coumarins and structurally related compounds have been recently shown to inhibit replication of human immunodeficiency virus (HIV) and thus, exhibit a therapeutic potential. In this study we report that mesuol and isomesuol, two 4-phenyl coumarins, isolated from the tree Marila pluricostata, suppress HIV-1 replication...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2005.02.006
更新日期：2005-06-01 00:00:00
abstract：:Both classical swine fever (CSF) and pseudorabies are highly contagious, economically significant diseases of swine in China. Although vaccination with the C-strain against classical swine fever virus (CSFV) is widely carried out and severe outbreaks of CSF seldom occur in China, CSF is sporadic in many pig herds and ...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2019.104652
更新日期：2020-01-01 00:00:00
abstract：:Sequences from the gag, pol and rev regions of the RF strain of HIV-1 (HIV-1RF) were chosen as targets for antisense phosphorothioate oligodeoxynucleotides (S-oligos). These sequences were the p18/p24 junction in gag, the active site of HIV protease in pol; a sequence from the first exon of the rev gene and S-oligodeo...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/0166-3542(92)90090-r
更新日期：1992-01-01 00:00:00
abstract：:Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and reduces the risk of cytomegalovirus (CMV) infection in transplant recipients. Everolimus inhibits mTOR complex 1, which regulates factors involved in several crucial cellular functions and is required for CMV replication. However, it is not clear h...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2018.12.004
更新日期：2019-02-01 00:00:00
abstract：:Respiratory syncytial virus (RSV) infection causes significant disease in the lower respiratory tract of young children, and there is currently no licensed vaccine to prevent RSV infection. The F glycoprotein is considered a major antigenic target for RSV vaccine development. Recent evidence indicates that the pre-fus...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2019.02.017
更新日期：2019-05-01 00:00:00
abstract：:Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In t...
journal_title：Antiviral research
pub_type： 杂志文章
doi：10.1016/j.antiviral.2015.10.019
更新日期：2016-02-01 00:00:00
