Effect of influenza H1N1 neuraminidase V116A and I117V mutations on NA activity and sensitivity to NA inhibitors
Publication date: Available online 19 June 2019Source: Antiviral ResearchAuthor(s): Simone E. Adams, Nicolette Lee, Vladimir Y. Lugovtsev, Anastasia Kan, Raymond P. Donnelly, Natalia A. IlyushinaAbstractNeuraminidase inhibitors (NAIs) play a key role in the management of influenza. Given the limited number of FDA-approved anti-influenza drugs, evaluation of potential drug-resistant variants is of high priority. Two NA mutations, V116A and I117V, are found in ∼0.6% of human, avian, and swine N1 isolates. Using the A/California/04/09-like (CA/04, H1N1) background, we examined the impact of V116A and I117V NA mutations on...
Source: Antiviral Therapy - June 20, 2019 Category: Virology Source Type: research

Modifications in the branched arms of a class of dual inhibitors OF HIV and EV71 replication expand their antiviral spectrum
Publication date: Available online 20 June 2019Source: Antiviral ResearchAuthor(s): Belén Martínez-Gualda, Liang Sun, Carmen Mirabelli, Leen Delang, Johan Neyts, Dominique Schols, María-José Camarasa, Ana San-FélixAbstractWe 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 of dendrimers with divalent and tetravalent branched ...
Source: Antiviral Therapy - June 20, 2019 Category: Virology Source Type: research

Anti-HBV activity of retinoid drugs in vitro versus in vivo
We describe here the anti-HBV activity of natural and synthetic retinoids in primary human hepatocytes (PHHs). The most potent compounds inhibited HBsAg, HBeAg, viral RNA and DNA production by HBV infected cells with EC50 values ranging from 0.4 to 2.6 μM. The activity was independent of PHH donor and HBV genotype used in testing. 13-cis retinoic acid (Accutane) was selected for further evaluation in the PXB chimeric mouse model of HBV infection at doses allowing to achieve Accutane peak serum concentrations near its antiviral EC90 and exposures ∼5-fold higher than a typical clinical dose. While these supraclinica...
Source: Antiviral Therapy - June 20, 2019 Category: Virology Source Type: research

Persistent primary cytomegalovirus infection in a kidney transplant recipient: Multi-drug resistant and compartmentalized infection leading to graft loss
We describe a case of a 43-year-old CMV-seronegative patient who underwent kidney transplantation from a CMV-seropositive donor and developed CMV disease despite valganciclovir prophylaxis. CMV viral load increased even though valgangiclovir dose was augmented and immunosuppressive therapy reduced. CMV genotyping revealed mutations in the viral UL97 protein kinase, explaining ganciclovir-resistant CMV infection. The viral load failed to respond to foscavir, cidofovir and CMV-neutralizing immunoglobulins. Kidney allograft dysfunction developed 3 months post-transplantation with a histopathologic diagnosis of CMV neph...
Source: Antiviral Therapy - June 17, 2019 Category: Virology Source Type: research

Bardoxolone methyl as a novel potent antiviral agent against hepatitis B and C viruses in human hepatocyte cell culture systems.
In this study, the potential of bardoxolone methyl (BARD), an Nrf2 activator, was examined in cell culture systems against HBV and HCV. We investigated that BARD had a suppressive effect on the production of extracellular HBV DNA in several HBV culture systems. In addition, BARD treatment reduced the levels of intracellular HBV pregenome RNA (pgRNA), a transcript from the HBV genome and a template of HBV genome replication. HCV genome replication was also suppressed in HCV subgenomic replicon-bearing cells by BARD treatment. BARD might be a novel treatment for patients with HBV and HCV co-infection. (Source: Antiviral Therapy)
Source: Antiviral Therapy - June 15, 2019 Category: Virology Source Type: research

Structure of the yellow fever NS5 protein reveals conserved drug targets shared among flaviviruses
Publication date: Available online 13 June 2019Source: Antiviral ResearchAuthor(s): Anna Dubankova, Evzen BouraAbstractYellow fever virus (YFV) is responsible for devastating outbreaks of Yellow fever (YF) in humans and is associated with high mortality rates. Recent large epidemics and epizootics and exponential increases in the numbers of YF cases in humans and non-human primates highlight the increasing threat YFV poses, despite the availability of an effective YFV vaccine. YFV is the first human virus discovered, but the structures of several of the viral proteins remain poorly understood. Here we report the structure ...
Source: Antiviral Therapy - June 14, 2019 Category: Virology Source Type: research

T-705 induces lethal mutagenesis in Ebola and Marburg populations in macaques
This study expands our understanding of MOAs of these compounds for the Filovirus family and provides further evidence that lethal mutagenesis could be a preponderant MOA for this class of therapeutic compounds. (Source: Antiviral Therapy)
Source: Antiviral Therapy - June 11, 2019 Category: Virology Source Type: research

Input of recombinant phenotyping for the characterization of a novel acyclovir-resistance mutation identified in a patient with recurrent herpetic keratitis
We report here a case of an immunocompetent patient suffering from recurrent epithelial herpetic keratitis associated with the emergence of antiviral resistance. Indeed, the not previously described amino acid change L340R within herpes simplex virus thymidine kinase, was shown to confer acyclovir-resistance by recombinant phenotyping using bacmid technology. (Source: Antiviral Therapy)
Source: Antiviral Therapy - June 11, 2019 Category: Virology Source Type: research

The development and approval of tecoviromat (TPOXX®), the first antiviral against smallpox
Publication date: Available online 7 June 2019Source: Antiviral ResearchAuthor(s): Michael Merchlinsky, Andrew Albright, Victoria Olson, Helen Schiltz, Tyler Merkeley, Claiborne Hughes, Brett Petersen, Mark ChallbergAbstractThe classification of smallpox by the U.S. Centers for Disease Control and Prevention (CDC) as a Category A Bioterrorism threat agent has resulted in the U.S. Government investing significant funds to develop and stockpile a suite of medical countermeasures to ameliorate the consequences of a smallpox epidemic. This stockpile includes both vaccines for prophylaxis and antivirals to treat symptomatic pat...
Source: Antiviral Therapy - June 8, 2019 Category: Virology Source Type: research

Regulation of influenza a virus mRNA splicing by CLK1
Publication date: Available online 6 June 2019Source: Antiviral ResearchAuthor(s): Anita Artarini, Michael Meyer, Yu Jin Shin, Kilian Huber, Nikolaus Hilz, Franz Bracher, Daniel Eros, Laszlo Orfi, Gyorgy Keri, Sigrid Goedert, Martin Neuenschwander, Jens von Kries, Yael Domovich-Eisenberg, Noa Dekel, István Szabadkai, Mario Lebendiker, Zoltán Horváth, Tsafi Danieli, Oded Livnah, Olivier MoncorgéAbstractInfluenza A virus carries eight negative single-stranded RNAs and uses spliced mRNAs to increase the number of proteins produced from them. Several genome-wide screens for essential host factors fo...
Source: Antiviral Therapy - June 7, 2019 Category: Virology Source Type: research

A quantitative method for hepatitis B virus covalently closed circular DNA enables distinguishing direct acting antivirals from cell-targeting reagents
Publication date: Available online 5 June 2019Source: Antiviral ResearchAuthor(s): Zhenchao Gao, Liwei Yan, Wenhui LiAbstractStudying the biogenesis of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and developing anti-HBV agents both require analytical methods to quantify viral DNA levels inside host cells. The well-accepted Southern blotting method is only semi-quantitative, while the other widely used methods (based on qPCR) have been questioned as to their fidelity for cccDNA quantification. In addition, Southern blotting and qPCR results barely reflect the number of host cells present in an analytical...
Source: Antiviral Therapy - June 6, 2019 Category: Virology Source Type: research

Small molecule ONC201 inhibits HIV-1 replication in macrophages via FOXO3a and TRAIL
Publication date: Available online 31 May 2019Source: Antiviral ResearchAuthor(s): Runze Zhao, Yuju Li, Santhi Gorantla, Larisa Y. Poluektova, Hai Lin, Fengtong Gao, Hongyun Wang, Jeffrey Zhao, Jialin C. Zheng, Yunlong HuangAbstractDespite the success of antiretroviral therapy (ART), eradication of HIV-1 from brain reservoirs remains elusive. HIV-1 brain reservoirs include perivascular macrophages that are behind the blood-brain barrier and difficult to access by ART. Macrophages express transcription factor FOXO3a and the TNF superfamily cytokine TRAIL, which are known to target HIV-1-infected macrophages for viral inhibi...
Source: Antiviral Therapy - June 1, 2019 Category: Virology Source Type: research

Added value of ultra-deep sequencing (UDS) approach for detection of genotypic antiviral resistance of herpes simplex virus (HSV)
Publication date: Available online 31 May 2019Source: Antiviral ResearchAuthor(s): Mélanie Mercier-Darty, David Boutolleau, Christophe Rodriguez, Sonia BurrelAbstractClassically, Sanger sequencing is considered the gold standard for detection of HSV drug resistance mutations (DRMs). As a complementary method, ultra-deep sequencing (UDS) has an improved ability to detect minor variants and mixed populations. The aim of this work was to apply UDS performed on MiSeq® Illumina platform to the detection of HSV DRMs and to the evaluation of the subpopulation diversity in clinical samples in comparison with Sanger sequ...
Source: Antiviral Therapy - June 1, 2019 Category: Virology Source Type: research

Heterologous prime-boost immunization with vesiculovirus-based vectors expressing HBV core antigen induces CD8+ T cell responses in naïve and persistently infected mice and protects from challenge
In this study, we evaluated the immunogenicity and efficacy of two attenuated vesiculovirus-based platforms expressing HBV Core antigen, the highly attenuated vesicular stomatitis virus (VSV) N4CT1 and a unique vaccine platform [virus-like vesicles (VLV)] that is based on a Semliki Forest virus replicon expressing the VSV glycoprotein. We found that heterologous prime-boost immunization with VLV and N4CT1 induced specific CD8+ T cell responses to Core in naïve mice. When immunized mice were later challenged with AAV-HBV, functional Core-specific CD8+ T cells were present in the liver, and mice were protected from esta...
Source: Antiviral Therapy - May 31, 2019 Category: Virology Source Type: research

Hepatitis C virus and cumulative infections are associated with atherogenic cardiovascular events in HIV-infected subjects
Conclusionsboth HCV and the burden of infections are associated with an increased risk of cardivascular event in HIV-infected patients, together with other cardiovascular risk factors. Therapeutic strategies such as HCV erradication or VZV immunization could ameliorate cardiovascular risk in these subjects. (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 31, 2019 Category: Virology Source Type: research

Editorial Board
Publication date: July 2019Source: Antiviral Research, Volume 167Author(s): (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 31, 2019 Category: Virology Source Type: research

UL23, UL30, and UL5 characterization of HSV1 clinical strains isolated from hematology department patients
Publication date: Available online 30 May 2019Source: Antiviral ResearchAuthor(s): Thibault Labrunie, Sophie Ducastelle, Carine Domenech, Florence Ader, Florence Morfin, Emilie FrobertAbstractGenotypic diagnosis of HSV drug resistance can be performed routinely in a clinically relevant time. Nevertheless, data about HSV mutations (polymorphism or resistance) is not exhaustive which hinders the interpretation of such tests. The UL23, UL30, and UL5 genes are of greatest interest as these encode, respectively, thymidine kinase, DNA polymerase, and helicase, which, if mutated may affect the effectiveness of acyclovir, foscarne...
Source: Antiviral Therapy - May 30, 2019 Category: Virology Source Type: research

Development of a rapid antiviral screening assay based on eGFP reporter virus of Mayaro virus
Publication date: Available online 29 May 2019Source: Antiviral ResearchAuthor(s): Xiaodan Li, Hongqing Zhang, Yanan Zhang, Jiaqi Li, Zhen Wang, Chenglin Deng, Ana Carolina Gomes Jardim, Ana Carolina B. Terzian, Maurício Lacerda Nogueira, Bo ZhangAbstractMayaro virus (MAYV) is a neglected mosquito-borne alphavirus that causes illness similar to Chikungunya (CHIKV), Dengue (DENV) and Zika virus (ZIKV). Currently, there is no specific treatment or vaccine against MAYV infection. To develop an efficient antiviral screening assay for MAYV, we constructed the infectious clones of MAYV strain BeAr 20290 and its eGFP repor...
Source: Antiviral Therapy - May 29, 2019 Category: Virology Source Type: research

The efficacy of inactivated split respiratory syncytial virus as a vaccine candidate and the effects of novel combination adjuvants
This study demonstrates the efficacy of Split RSV as an effective vaccine candidate. (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 28, 2019 Category: Virology Source Type: research

Heterologous expression of human norovirus GII.4 VP1 leads to assembly of T=4 virus-like particles
In this study, the VLP structures of two norovirus GII.4 genetic variants that were identified in 1976 and 2012 were determined using cryo-EM. Surprisingly, we found that greater than 95% of these GII.4 VLPs were larger than virions and 3D reconstruction showed that these VLPs exhibited T = 4 icosahedral symmetry. We also discovered that the T = 4 VLPs presented several novel structural features. The T = 4 particles assembled from 240 copies of VP1 that adopted four quasi-equivalent conformations (A, B, C, and D) that formed two distinct dimers, A/B and C/D. The protruding domains were elevated ∼21 Å...
Source: Antiviral Therapy - May 27, 2019 Category: Virology Source Type: research

Characterization of substitutions in the neuraminidase of A(H7N9) influenza viruses selected following serial passage in the presence of different neuraminidase inhibitors
Publication date: Available online 25 May 2019Source: Antiviral ResearchAuthor(s): R. Farrukee, J. Butler, P.C. Reading, A.C. HurtAbstract:Avian A(H7N9) infections in humans have been reported in China since 2013 and are of public health concern due to their severity and pandemic potential. Oseltamivir and peramivir are neuraminidase inhibitors (NAIs) routinely used for the treatment of A(H7N9) infections, but variants with reduced sensitivity to these drugs can emerge in patients during treatment. Zanamivir and laninamivir are NAIs that are used less frequently. Herein, we performed in vitro serial passaging experiments w...
Source: Antiviral Therapy - May 25, 2019 Category: Virology Source Type: research

Amidic derivatives of valproic acid, valpromide and valnoctamide, inhibit HSV-1 infection in oligodendrocytes
Publication date: Available online 25 May 2019Source: Antiviral ResearchAuthor(s): B. Praena, R. Bello-Morales, F. de Castro, J.A. López-GuerreroAbstractHerpes simplex virus type 1 (HSV-1) is a ubiquitous infectious agent that can establish latency in neurons, and in some cases, viral retrograde transport results in infection of the central nervous system (CNS). Several antivirals have been identified with the ability to inhibit HSV-1 replication in human cells to a greater or lesser degree, most of which are nucleoside analogues that unfortunately exhibit teratogenic potential, embryotoxicity, carcinogenic or antip...
Source: Antiviral Therapy - May 25, 2019 Category: Virology Source Type: research

Longitudinal effects of Nucleos(t)ide analogue therapy in chronic hepatitis B patients and the utility of non-invasive fibrosis markers during treatment: A single-center experience for up to 17 years
ConclusionEarly dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment. (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 23, 2019 Category: Virology Source Type: research

Virucidal activity of proanthocyanidin against Mayaro virus
Publication date: Available online 21 May 2019Source: Antiviral ResearchAuthor(s): Ariane Coelho Ferraz, Thaís de Fátima Silva Moraes, Waleska Stephanie da Cruz Nizer, Michelli dos Santos, Antônio Helvécio Tótola, Jaqueline Maria Siqueira Ferreira, Sidney Augusto Viera-Filho, Vanessa Gonçalves Rodrigues, Lucienir Pains Duarte, Cintia Lopes de Brito Magalhães, José Carlos de MagalhãesAbstractMayaro virus (MAYV) is a sublethal arbovirus transmitted by mosquitoes with possible installation of an urban cycle in the Americas. Its infection causes disabling arthralgia...
Source: Antiviral Therapy - May 23, 2019 Category: Virology Source Type: research

Phylogenetically based establishment of a dengue virus panel, representing all available genotypes, as a tool in dengue drug discovery
Publication date: Available online 11 May 2019Source: Antiviral ResearchAuthor(s): Franck Touret, Cécile Baronti, Olivia Goethals, Marnix Van Loock, Xavier de Lamballerie, Gilles QueratAbstractDengue fever is the most widespread of the human arbovirus diseases, with approximately one third of the world's population at risk of infection. Dengue viruses are members of the genus Flavivirus (family Flaviviridae) and, antigenically, they separate as four closely related serotypes (1–4) that share 60–75% amino acid homology. This genetic diversity complicates the process of antiviral drug discovery. Thus, curr...
Source: Antiviral Therapy - May 12, 2019 Category: Virology Source Type: research

Dual targeting of dengue virus virions and NS1 protein with the heparan sulfate mimic PG545
Publication date: Available online 11 May 2019Source: Antiviral ResearchAuthor(s): Naphak Modhiran, Neha S. Gandhi, Norbet Wimmer, Stacey Cheung, Katryn Stacey, Paul R. Young, Vito Ferro, Daniel WattersonAbstractDengue virus (DENV) is the most prevalent mosquito-borne flavivirus that infects humans. At present, there are no specific antiviral drugs to treat DENV infection and vaccine development has met with challenges. DENV encodes two glycosaminoglycan (GAG) binding proteins; Envelope (E) and non-structural protein 1 (NS1). While previous work has validated the use of GAG analogues as inhibitors of E mediated virus-cell ...
Source: Antiviral Therapy - May 12, 2019 Category: Virology Source Type: research

Toll-like receptor 5 agonist flagellin reduces Influenza A Virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir
This study evaluated the ability of flagellin, agonist of Toll-like receptor 5 (TLR5), to control the replication of influenza A virus (IAV) in mice. First, we showed that systemic or intranasal administration of flagellin activated transcription of anti-viral genes in lung tissue. Prophylactic and therapeutic flagellin administration resulted in decreased levels of viral RNA and infectious virus in the lungs of H3N2 IAV-infected mice. The effect of the flagellin on viral replication was also observed in Ifnar-/- and Il22-/- IAV-infected mice, suggesting a mechanism independent of type I interferon and interleukin 22 signa...
Source: Antiviral Therapy - May 10, 2019 Category: Virology Source Type: research

Dual effect of the broad spectrum kinase inhibitor midostaurin in acute and latent HIV-1 infection
Publication date: Available online 8 May 2019Source: Antiviral ResearchAuthor(s): Edurne Garcia-Vidal, Roger Badia, Maria Pujantell, Marc Castellví, Eudald Felip, Bonaventura Clotet, Eva Riveira-Muñoz, Ester Ballana, José A. EstéAbstractMidostaurin is a multi-kinase inhibitor with antineoplastic activity. We assessed the capacity of midostaurin to affect early and late steps of HIV-1 infection and to reactivate HIV-1 latently infected cells, alone or in combination with histone deacetylase inhibitors (HDACi) known to act as latency-reversing agents (LRA). Acute HIV-1 infection was assessed by fl...
Source: Antiviral Therapy - May 10, 2019 Category: Virology Source Type: research

Editorial Board
Publication date: June 2019Source: Antiviral Research, Volume 166Author(s): (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 10, 2019 Category: Virology Source Type: research

Insect anionic septapeptides suppress DENV replication by activating antiviral cytokines and miRNAs in primary human monocytes
In conclusion, anionic septapeptides exerted anti-DENV activity in human monocytes through the upregulation of innate immune responses and the activation of several previously reported antiviral and inflammation-related miRNAs. (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 9, 2019 Category: Virology Source Type: research

Recombinant live attenuated influenza vaccine viruses carrying CD8 T-cell epitopes of respiratory syncytial virus protect mice against both pathogens without inflammatory disease
Publication date: Available online 7 May 2019Source: Antiviral ResearchAuthor(s): Tatiana Kotomina, Irina Isakova-Sivak, Victoria Matyushenko, Ki-Hye Kim, Youri Lee, Yu-Jin Jung, Sang-Moo Kang, Larisa RudenkoAbstractRespiratory syncytial virus (RSV) is the most common cause of lower respiratory disease in young children, elderly and immunocompromised adults. There is no licensed vaccine against RSV although development of an effective and safe RSV vaccine has been a high priority for several decades. Among the various vaccine platforms, the viral-vectored RSV vaccines based on licensed cold-adapted live attenuated influenz...
Source: Antiviral Therapy - May 9, 2019 Category: Virology Source Type: research

Mitophagy in human astrocytes treated with the antiretroviral drug Efavirenz: Lack of evidence or evidence of the lack
In conclusion, these findings add to the existing knowledge of the EFV-triggered mitochondrial interference, a mechanism that may be implicated in the adverse CNS events observed in the clinics.Graphical abstract (Source: Antiviral Therapy)
Source: Antiviral Therapy - May 9, 2019 Category: Virology Source Type: research

Kinase inhibitors Tyrphostin 9 and rottlerin block early steps of rabies virus cycle
Publication date: Available online 7 May 2019Source: Antiviral ResearchAuthor(s): Zoé Lama, Yves Gaudin, Danielle Blondel, Cécile Lagaudriere-GesbertAbstractRabies virus (RABV) is a neurotropic virus that causes fatal encephalitis in humans and animals and still kills up to 59,000 people worldwide every year. To date, only preventive or post-exposure vaccination protects against the disease but therapeutics are missing. After screening a library of 80 kinases inhibitors, we identified two compounds as potent inhibitors of RABV infection: Tyrphostin 9 and Rottlerin. Mechanism of action studies show that both i...
Source: Antiviral Therapy - May 7, 2019 Category: Virology Source Type: research

Assessing the utility of antivirals for preventing maternal-fetal transmission of zika virus in pregnant mice
In this study, we developed a mouse model of ZIKV infection that specifically establishes vertical maternal-fetal transmission of ZIKV in 40–60% of fetuses when the dams acquire ZIKV infection during pregnancy. This mouse model somewhat mirrors the experience in humans at the peak of the epidemic in the Americas. Using this model, we demonstrate that a well-documented directly acting antiviral (DAA) compound that targets flaviviral RNA synthesis can completely prevent fetal infection when the treatment is started at the time of infection. Notably, we show that the treatment commenced at the time of peak viremia is st...
Source: Antiviral Therapy - May 2, 2019 Category: Virology Source Type: research

Curcumin is an APE1 redox inhibitor and exhibits an antiviral activity against KSHV replication and pathogenesis
Publication date: Available online 26 April 2019Source: Antiviral ResearchAuthor(s): He Li, Canrong Zhong, Qian Wang, Weikang Chen, Yan YuanAbstractCurcumin, a polyphenol, is the main bioactive compound in dietary spice turmeric curcuma longa). It possesses anti-inflammatory, anti-oxidant and anti-neoplastic properties and shows potentials in treating or preventing particular diseases such as oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, hyperlipidemia and cancers. The diverse range and potential health beneficial effects has generated enthusiasm leading to intensive investigation into the ...
Source: Antiviral Therapy - April 27, 2019 Category: Virology Source Type: research

Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV
In this study, using a computational and structural based drug design approach, we have discovered an effective HIV -1 NNRTI, compound I (Cmpd I) that is very potent in biochemical assays and which targets key residues in the allosteric binding pocket of wild-type (WT)-RT as revealed by structural studies. Furthermore, Cmpd I exhibited very potent antiviral activity in HIV-1 infected T cells, lacked cytotoxicity (therapeutic index>100,000), and no significant off-target effects were noted in pharmacological assays. To address the issue of non-adherence, we developed a long-acting nanoformulation of Cmpd I (Cmpd I-NP) us...
Source: Antiviral Therapy - April 27, 2019 Category: Virology Source Type: research

The retinoic acid receptor (RAR) α-specific agonist Am80 (tamibarotene) and other RAR agonists potently inhibit hepatitis B virus transcription from cccDNA
In conclusion, our results indicate a persistent inhibition of HBV transcription by Am80, which might be used for drug repositioning. (Source: Antiviral Therapy)
Source: Antiviral Therapy - April 22, 2019 Category: Virology Source Type: research

A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection: A proof-of-concept study
This study investigates the HIV prevention potency of a novel long-acting BIC nano-formulation aimed to improve adherence. Poly (lactic-co-glycolic acid) loaded BIC nanoparticles (BIC NPs) were formulated using an oil-in-water emulsion methodology. BIC NPs were
Source: Antiviral Therapy - April 15, 2019 Category: Virology Source Type: research

Inhibition of African swine fever virus infection by genkwanin
Publication date: Available online 13 April 2019Source: Antiviral ResearchAuthor(s): Astghik Hakobyan, Erik Arabyan, Armen Kotsinyan, Zaven Karalyan, Harutyun Sahakyan, Vahram Arakelov, Karen Nazaryan, Fernando Ferreira, Hovakim ZakaryanAbstractAfrican swine fever virus (ASFV) is the causative agent of an economically important disease of pigs for which no effective vaccines or antiviral drugs are available. Recent outbreaks in EU countries and China have highlighted the critical role of antiviral research in combating this disease. We have previously shown that apigenin, a naturally occurring plant flavone, possesses sign...
Source: Antiviral Therapy - April 13, 2019 Category: Virology Source Type: research

Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference
Publication date: Available online 8 April 2019Source: Antiviral ResearchAuthor(s): John H. Beigel, Hannah H. Nam, Peter L. Adams, Amy Krafft, William L. Ince, Samer S. El-Kamary, Amy C. SimsAbstractThe International Society for Influenza and other Respiratory Virus Diseases held its 6th Antiviral Group (isirv-AVG) conference in Rockville, Maryland, November 13–15, 2018. The three-day program was focused on therapeutics towards seasonal and pandemic influenza, respiratory syncytial virus, coronaviruses including MERS-CoV and SARS-CoV, human rhinovirus, and other respiratory viruses. Updates were presented on several ...
Source: Antiviral Therapy - April 10, 2019 Category: Virology Source Type: research

Efficacy of a ML336 derivative against Venezuelan and eastern equine encephalitis viruses
We report findings from in vitro assessments of four analogs of ML336, and in vivo screening of three of these new derivatives, BDGR-4, BDGR-69 and BDGR-70. The optimal dosing for maximal protection was observed at 12.5 mg/kg/day, twice daily for 8 days. BDGR-4 was tested further for prophylactic and therapeutic efficacy in mice challenged with VEEV Trinidad Donkey (TrD). Mice challenged with VEEV TrD showed 100% and 90% protection from lethal disease when treated at 24 and 48 h post-infection, respectively. We also measured 90% protection for BDGR-4 in mice challenged with Eastern equine encephalitis virus. In additio...
Source: Antiviral Therapy - April 8, 2019 Category: Virology Source Type: research

Suppression of pyrimidine biosynthesis by targeting DHODH enzyme robustly inhibits rotavirus replication
In this study, we demonstrated that two specific DHODH enzyme inhibitors, brequinar (BQR) and leflunomide (LFM) robustly inhibited rotavirus replication in conventional human intestinal Caco2 cell line as well as in human primary intestinal organoids. The antiviral effect is conserved in both laboratory strain SA11 and rotavirus strain 2011K isolated from clinical sample. Mechanistic study indicated that BQR and LFM exerted their anti-rotavirus effect through targeting DHODH to deplete pyrimidine nucleotide pool. Therefore, targeting pyrimidine biosynthesis represents a potential approach for developing antiviral strategie...
Source: Antiviral Therapy - April 8, 2019 Category: Virology Source Type: research

Antiviral activity of pinocembrin against Zika virus replication
This study has demonstrated for the first time the in vitro anti-ZIKV activity of pinocembrin.Graphical abstract (Source: Antiviral Therapy)
Source: Antiviral Therapy - April 6, 2019 Category: Virology Source Type: research

Identification of a clinical compound losmapimod that blocks Lassa virus entry
In this study, we identified losmapimod, a p38 mitogen-activated protein kinase (MAPK) inhibitor, from 102 screened compounds as an inhibitor of LASV infection. Losmapimod exerted its inhibitory effect against LASV after p38 MAPK down-regulation, and, interestingly, had no effect on other arenaviruses capable of causing viral hemorrhagic fever. Mechanistic studies showed that losmapimod inhibited LASV entry by affecting the stable signal peptide (SSP)-GP2 subunit interface of the LASV glycoprotein, thereby blocking pH-dependent viral fusion. As an aryl heteroaryl bis-carboxyamide derivative, losmapimod represents a novel c...
Source: Antiviral Therapy - April 5, 2019 Category: Virology Source Type: research

New antiviral approaches for human parainfluenza: Inhibiting the haemagglutinin-neuraminidase
We describe past and present hPIV HN inhibition strategies based on sialic acid scaffolds, together with other novel approaches that decrease hPIV infectivity. Although many HN inhibitors have been developed and evaluated as anti-hPIV agents, currently only a host-directed therapy (DAS181) has succeeded in phase II clinical drug trials. Hence, the review concludes with future considerations for targeting the specific function(s) of hPIV HN and suggestions for antiviral drug design. (Source: Antiviral Therapy)
Source: Antiviral Therapy - April 4, 2019 Category: Virology Source Type: research

Cell line-dependent activation and antiviral activity of T-1105, the non-fluorinated analogue of T-705 (favipiravir)
Publication date: Available online 2 April 2019Source: Antiviral ResearchAuthor(s): Johanna Huchting, Evelien Vanderlinden, Ria Van Berwaer, Chris Meier, Lieve NaesensAbstractThe antiviral drug T-705 (favipiravir) and its non-fluorinated analogue T-1105 inhibit the polymerases of RNA viruses after being converted to their ribonucleoside triphosphate (RTP) metabolite. We here compared the activation efficiency of T-705 and T-1105 in four cell lines that are commonly used for their antiviral evaluation. In MDCK cells, the levels of T-705-RTP were markedly lower than those of T-1105-RTP, while the opposite was seen in A549, V...
Source: Antiviral Therapy - April 2, 2019 Category: Virology Source Type: research

Genomic signature of early T-cell response is associated with lower antibody titer threshold for sterilizing immunity
Publication date: Available online 30 March 2019Source: Antiviral ResearchAuthor(s): Eugenia Z. Ong, Esther S. Gan, Ruklanthi de Alwis, Limin Wijaya, Xin Mei Ong, Menglan Zhang, Abigail WL. Wong, Yin Bun Cheung, Raphaël M. Zellweger, Eng Eong Ooi, Jenny G. LowAbstractVaccination is an effective approach to reduce disease burden. High vaccination coverage blocks pathogen transmission to ensure herd immunity. However, the concept of herd immunity assumes that vaccinated individuals cannot be infected and mediate silent pathogen transmission. While the correlates of vaccine-mediated protection against disease have been e...
Source: Antiviral Therapy - April 1, 2019 Category: Virology Source Type: research

Drug repurposing of N-acetyl cysteine as antiviral against dengue virus infection
Publication date: Available online 27 March 2019Source: Antiviral ResearchAuthor(s): Gopinathan Pillai Sreekanth, Jutatip Panaampon, Aroonroong Suttitheptumrong, Aporn Chuncharunee, Jintana Bootkunha, Pa-thai Yenchitsomanus, Thawornchai LimjindapornAbstractLiver injury is one of the hallmark features of severe dengue virus (DENV) infection since DENV can replicate in the liver and induce hepatocytes to undergo apoptosis. N-acetyl cysteine (NAC), which is a clinically-used drug for treating acetaminophen toxicity, was found to benefit patients with DENV-induced liver injury; however, its mechanism of action remains unclear....
Source: Antiviral Therapy - March 29, 2019 Category: Virology Source Type: research

Oral immunization with bacteriophage MS2-L2 VLPs protects against oral and genital infection with multiple HPV types associated with head & neck cancers and cervical cancer
Publication date: Available online 26 March 2019Source: Antiviral ResearchAuthor(s): Lukai Zhai, Rashi Yadav, Nitesh K. Kunda, Dana Anderson, Elizabeth Bruckner, Elliott K. Miller, Rupsa Basu, Pavan Muttil, Ebenezer TumbanAbstractHuman papillomaviruses (HPVs) are the most common sexually transmitted infections. HPVs are transmitted through anogenital sex or oral sex. Anogenital transmission/infection is associated with anogenital cancers and genital warts while oral transmission/infection is associated with head and neck cancers (HNCs) including recurrent respiratory papillomatosis. Current HPV vaccines protect against HPV...
Source: Antiviral Therapy - March 27, 2019 Category: Virology Source Type: research

HIV “shock and kill” therapy: In need of revision
Publication date: Available online 23 March 2019Source: Antiviral ResearchAuthor(s): Erik Abner, Albert JordanAbstractThe implementation of antiretroviral therapy 23 years ago has rendered HIV infection clinically manageable. However, the disease remains incurable, since it establishes latent proviral reservoirs, which in turn can stochastically begin reproducing viral particles throughout the patient's lifetime. Viral latency itself depends in large part on the silencing environment of the infected host cell, which can be chemically manipulated. “Shock and kill” therapy intends to reverse proviral quiescence b...
Source: Antiviral Therapy - March 24, 2019 Category: Virology Source Type: research