Interaction of cyclophilin a and human coronavirus 229E N protein is essential for virus replication.
unn A Abstract The well-known immunosuppressive drug cyclosporin A inhibits replication of various viruses including coronaviruses by binding to cellular cyclophilins thus inactivating their cis-trans peptidyl-prolyl isomerase function. Viral nucleocapsid proteins are inevitable for genome encapsidation and replication. Here we demonstrate the interaction between the N protein of HCoV-229E and cyclophilin A, not cyclophilin B. Cyclophilin inhibitors abolish this interaction. Upon infection, cyclophilin A stays evenly distributed throughout the cell, whereas cyclophilin B concentrates at ER-bleb-like structures. We...
Source: Antiviral Research - October 18, 2019 Category: Virology Authors: Ma-Lauer Y, Zheng Y, Malešević M, von Brunn B, Fischer G, von Brunn A Tags: Antiviral Res Source Type: research

Virtual screening identified compounds that bind to cyclin dependent kinase 2 and prevent herpes simplex virus type 1 replication and reactivation in neurons.
This study identified compounds that dock to a model of cyclin dependent kinase 2 (CDK2), a cellular enzyme required for efficient HSV-1 replication, and have anti-HSV-1 activity. Compounds obtained from virtual screening by Pharmit were filtered in FAFDrugs4 for good pharmacokinetic and toxicological profiles and submitted to molecular docking on CDK2 using Autodock Vina. The six most promising compounds were evaluated for inhibiting lytic replication of HSV-1 wild-type and ACV-resistant strains on human fibroblasts. The compounds were also assayed for cytotoxicity. Compounds 1, 2 and 3 showed antiviral activity with EC50...
Source: Antiviral Research - October 18, 2019 Category: Virology Authors: Viegas DJ, Edwards TG, Bloom DC, Abreu PA Tags: Antiviral Res Source Type: research

No impact of previous NRTIs resistance in HIV positive patients switched to DTG+2NRTIs under virological control: Time of viral suppression makes the difference.
Abstract The accumulation of drug-resistance mutations on combined antiretroviral regimens (ART) backbone could affect the virological efficacy of the regimen. Our aim was to assess the impact of previous drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) on the probability of virological failure (VF) in patients, under virological control, who switched to dolutegravir (DTG)+2NRTIs regimens. All HIV-1 positive drug-experienced patients who started a regimen composed by DTG+2NRTIs [abacavir/lamivudine or tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)/emtricitabine (FTC)] in t...
Source: Antiviral Research - October 17, 2019 Category: Virology Authors: Giacomelli A, Lai A, Franzetti M, Maggiolo F, Di Giambenedetto S, Borghi V, Francisci D, Magnani G, Pecorari M, Monno L, Vicenti I, Lepore L, Lombardi F, Paolucci S, Rusconi S, ARCA collaborative group Tags: Antiviral Res Source Type: research

Hepatitis B virus replicating in hepatocellular carcinoma encodes HBx variants with preserved ability to antagonize restriction by Smc5/6.
In conclusion, in contrast to previous observations that tumor HBx variants lack transcriptional activity, we showed here that HBx variants have retained their ability to counteract Smc5/6 and thus to activate cccDNA transcription although they tend to lose antiproliferative activity. PMID: 31600532 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - October 7, 2019 Category: Virology Authors: Rivière L, Quioc-Salomon B, Fallot G, Halgand B, Féray C, Buendia MA, Neuveut C Tags: Antiviral Res Source Type: research

HDAC11 restricts HBV replication through epigenetic repression of cccDNA transcription.
In conclusion, HDAC11 restricts HBV replication through epigenetic repression of cccDNA transcription. These findings reveal the novel role of HDAC11 in HBV infection, further broadening our knowledge regarding the functions of HDAC11 and the roles of HDACs in the epigenetic regulation of HBV cccDNA. PMID: 31600533 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - October 7, 2019 Category: Virology Authors: Yuan Y, Zhao K, Yao Y, Liu C, Chen Y, Li J, Wang Y, Pei R, Chen J, Hu X, Zhou Y, Wu C, Chen X Tags: Antiviral Res Source Type: research

Development and characterization of two GP-specific monoclonal antibodies, which synergistically protect non-human primates against Ebola lethal infection.
atulin A, Logunov D, Naroditsky B, Gintsburg A Abstract Ebola fever is an acute highly contagious viral disease characterized by severe course, high mortality and development of hemorrhagic syndrome (tendency to skin hemorrhage and bleeding of mucous membranes). The mortality rate of the disease 60-90%. Nowadays, there are no licensed specific therapeutic agents for Ebola in the world. Monoclonal antibodies (MAbs) having viral neutralizing activity with high specificity to the GP protein of the Ebola virus are considered as candidate highly effective antiviral drugs. In our study, for the first time a panel of mou...
Source: Antiviral Research - October 5, 2019 Category: Virology Authors: Shcheblyakov D, Esmagambetov I, Simakin P, Kostina L, Kozlov A, Tsibezov V, Grebennikova T, Chifanov D, Rumyantseva I, Boyarskaya N, Sizikova T, Shagarova N, Andrus А, Shatohina I, Syromyatnikova S, Kovalchuk A, Pantyukhov V, Borisevich S, Zubkova O, Tuh Tags: Antiviral Res Source Type: research

Dipyridamole as a new drug to prevent Epstein-Barr virus reactivation.
cute;chal V Abstract Epstein-Barr virus (EBV) is a widely distributed gamma-herpesvirus that has been associated with various cancers mainly from lymphocytic and epithelial origin. Although EBV-mediated oncogenesis has been associated with viral oncogenes expressed during latency, a growing set of evidence suggested that antiviral treatments directed against EBV lytic phase may contribute to prevent some forms of cancers, including EBV-positive Post-Transplant Lymphoproliferative Diseases. It is shown here that dipyridamole (DIP), a safe drug with favorable and broad pharmacological properties, inhibits EBV reacti...
Source: Antiviral Research - September 30, 2019 Category: Virology Authors: Thomé MP, Borde C, Larsen AK, Henriques JAP, Lenz G, Escargueil AE, Maréchal V Tags: Antiviral Res Source Type: research

Novel UL97 drug resistance mutations identified at baseline in a clinical trial of maribavir for resistant or refractory cytomegalovirus infection.
Abstract In a Phase 2 clinical trial, 120 subjects with cytomegalovirus (CMV) infection refractory or resistant to standard therapy were randomized equally to 3 doses of oral maribavir treatment, and 70% achieved undetectable plasma CMV DNA within 12 weeks. At study entry, standard diagnostic UL97 genotyping was available for 71 subjects, with 60 (85%) revealing well-characterized ganciclovir resistance mutations that did not preclude a therapeutic response to maribavir. Central laboratory testing of a range of UL97 codons (288-468) not fully covered by standard genotyping was done on 93 subjects at baseline. This...
Source: Antiviral Research - September 27, 2019 Category: Virology Authors: Chou S, Wu J, Song K, Bo T Tags: Antiviral Res Source Type: research

Antiviral effects of simeprevir on multiple viruses.
This study thus demonstrates that the application of Simeprevir can be extended to other viruses besides HCV. PMID: 31563599 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 26, 2019 Category: Virology Authors: Li Z, Yao F, Xue G, Xu Y, Niu J, Cui M, Wang H, Wu S, Lu A, Zhong J, Meng G Tags: Antiviral Res Source Type: research

Octadecyloxyethyl benzyl tenofovir: A novel tenofovir diester provides sustained intracellular levels of tenofovir diphosphate.
Abstract Pre-exposure prophylaxis (PrEP) with topically or systemically administered antiretroviral agents can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials using tenofovir-containing agents, HIV-1 acquisition is reduced but not eliminated. Incomplete adherence remains the major contributor to failure. Sustained release or long-acting antiretroviral agents may provide better HIV-1 protection by reducing the clinical impact of incomplete adherence. To reduce dosing frequency, we synthesized a novel tenofovir prodrug, octadecyloxyethyl benzyl tenofovir (ODE...
Source: Antiviral Research - September 21, 2019 Category: Virology Authors: Beadle JR, Aldern KA, Zhang XQ, Valiaeva N, Hostetler KY, Schooley RT Tags: Antiviral Res Source Type: research

Ribonuclease H, an unexploited target for antiviral intervention against HIV and hepatitis B virus.
Abstract Ribonucleases H (RNases H) are endonucleolytic enzymes, evolutionarily related to retroviral integrases, DNA transposases, resolvases and numerous nucleases. RNases H cleave RNA in RNA/DNA hybrids and their activity plays an important role in the replication of prokaryotic and eukaryotic genomes, as well as in the replication of reverse-transcribing viruses. During reverse transcription, the RNase H activity of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) degrades the viral genomic RNA to facilitate the synthesis of viral double-stranded DNA. HIV and HBV reverse transcriptases contain DN...
Source: Antiviral Research - September 21, 2019 Category: Virology Authors: Tramontano E, Corona A, Menendez-Arias L Tags: Antiviral Res Source Type: research

GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 3: Epidemiological distribution of Mayaro virus.
X, GloPID-R chikungunya, o'nyong-nyong and Mayaro virus Working Group PMID: 31545981 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 20, 2019 Category: Virology Authors: Pezzi L, Rodriguez-Morales AJ, Reusken CB, Ribeiro GS, LaBeaud AD, Lourenço-de-Oliveira R, Brasil P, Lecuit M, Failloux AB, Gallian P, Jaenisch T, Simon F, Siqueira AM, Rosa-Freitas MG, Vega Rua A, Weaver SC, Drexler JF, Vasilakis N, de Lamballerie X, Gl Tags: Antiviral Res Source Type: research

GloPID-R report on chikungunya, o'nyong-nyong and Mayaro virus, part 2: Epidemiological distribution of o'nyong-nyong virus.
PMID: 31545982 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 20, 2019 Category: Virology Authors: Pezzi L, LaBeaud AD, Reusken CB, Drexler JF, Vasilakis N, Diallo M, Simon F, Jaenisch T, Gallian P, Sall A, Failloux AB, Weaver SC, de Lamballerie X, GloPID-R chikungunya, o'nyong-nyong and Mayaro virus Working Group Tags: Antiviral Res Source Type: research

Construction and characterization of Genotype-3 hepatitis C virus replicon revealed critical genotype-3-specific polymorphism for drug resistance and viral fitness.
In conclusion, we developed a novel genotype-3a subgenomic replicon by a functional screening approach, and revealed genotype-3-specfic amino acid residues that confer resistance to anti-NS3 DAAs while retaining viral fitness. PMID: 31542377 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 19, 2019 Category: Virology Authors: Guo M, Lu J, Gan T, Xiang X, Xu Y, Xie Q, Zhong J Tags: Antiviral Res Source Type: research

Artesunate derivative TF27 inhibits replication and pathogenesis of an oncogenic avian alphaherpesvirus.
In this study, we used this natural virus-host model for herpesvirus-induced cancer by infecting chickens with MDV, and evaluated the protective efficacy of TF27 and the nucleoside analogue valganciclovir (VGCV) on virus replication and tumorigenesis. We could demonstrate that both drugs reduced viral load in the blood and prevented tumor development in a large portion of the animals. Antiviral treatment also had a positive impact on body weight gain, while no negative compound-associated side effects were observed. This research provides the first evidence that the artesunate derivative TF27 and VGCV can be used in avian ...
Source: Antiviral Research - September 11, 2019 Category: Virology Authors: Bertzbach LD, Conradie AM, Hahn F, Wild M, Marschall M, Kaufer BB Tags: Antiviral Res Source Type: research

Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation.
Abstract As antiviral drug resistance develops and new viruses emerge there is a pressing need to develop strategies to rapidly develop antiviral therapeutics. Here we use phospho-specific flow cytometry to assess perturbations of many different cellular signaling pathways during treatment with drug combinations that are highly effective in blocking Herpes simplex virus type 1 (HSV-1) infection. We discovered two antiviral drug combinations act on distinct signaling pathways, either STAT1 or S6 phosphorylation, to block HSV-1 infection. We focused on upregulation of S6 phosphorylation by HSV-1 infection, and our s...
Source: Antiviral Research - September 9, 2019 Category: Virology Authors: Ding X, Krutzik PO, Ghaffari AA, Zhaozhi Y, Miranda D, Cheng G, Ho CM, Nolan GP, Sanchez DJ Tags: Antiviral Res Source Type: research

The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection.
Abstract The New World alphaviruses Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively) commonly cause a febrile disease that can progress to meningoencephalitis, resulting in significant morbidity and mortality. To address the need for a therapeutic agent for the treatment of Alphavirus infections, we identified and pursued preclinical characterization of a ribonucleoside analog EIDD-1931 (β-D-N4-hydroxycytidine, NHC), which has shown broad activity against alphaviruses in vitro and has a very high genetic barrier for development of resistance. To be truly effecti...
Source: Antiviral Research - September 5, 2019 Category: Virology Authors: Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, Guthrie DB, Hager M, Kuiper DL, Lockwood MA, Mitchell DG, Natchus MG, Sticher ZM, Kolykhalov AA Tags: Antiviral Res Source Type: research

Genetic stability of live-attenuated Zika vaccine candidates.
Abstract Zika virus (ZIKV) has drawn global attention as the etiologic agent of Zika Congenital Syndrome in babies born to infected pregnant women. To prevent future ZIKV outbreaks and protect persons at risk for severe disease, we developed two live-attenuated vaccine (LAV) candidates containing 10- or 20-nucleotide deletions in the 3'UTR of the viral genome (Δ10 and Δ20). After a single-dose immunization, both Δ10 and Δ20 LAVs protected mice and non-human primates against ZIKV infection. Here, we characterized the stability, safety, and efficacy of the LAVs after continuously culturing th...
Source: Antiviral Research - September 4, 2019 Category: Virology Authors: Muruato AE, Shan C, Fontes-Garfias CR, Liu Y, Gao Q, Weaver SC, Shi PY Tags: Antiviral Res Source Type: research

Formalin treatment increases the stability and immunogenicity of coxsackievirus B1 VLP vaccine.
This study demonstrates that formalin treatment increases the stability and immunogenicity of CVB1-VLP vaccine and may offer a universal tool for the stabilization of VLPs in the production of more efficient vaccines. PMID: 31491431 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - September 3, 2019 Category: Virology Authors: Hankaniemi MM, Stone VM, Andrejeff T, Heinimäki S, Sioofy-Khojine AB, Marjomäki V, Hyöty H, Blazevic V, Flodström-Tullberg M, Hytönen VP, Laitinen OH Tags: Antiviral Res Source Type: research

Cholesterol-conjugated stapled peptides inhibit Ebola and Marburg viruses in vitro and in vivo.
S Abstract The Filoviridae family consists of five ebolavirus species, Ebola (EBOV), Sudan (SUDV), Bundibugyo virus (BDBV), Reston (RESTV), and Taï Forest (TAFV) viruses, and a Marburgvirus species, with Marburg (MARV) and Ravn (RAVV) viruses. Ebola virus (EBOV) has emerged as a significant public health concern since the 2013-2016 Ebola Virus Disease outbreak in Western Africa. Currently, there are no therapeutics approved and the need for Ebola-specific therapeutics remains a gap. In search for anti-Ebola therapies we tested the idea of using inhibitory properties of peptides corresponding to the C-terminal...
Source: Antiviral Research - August 29, 2019 Category: Virology Authors: Pessi A, Bixler SL, Soloveva V, Radoshitzky S, Retterer C, Kenny T, Zamani R, Gomba G, Gharabeih D, Wells J, Wetzel KS, Warren TK, Donnelly G, Van Tongeren SA, Steffens J, Duplantier AJ, Kane CD, Vicat P, Couturier V, Kester KE, Shiver J, Carter K, Bavari Tags: Antiviral Res Source Type: research

Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation.
In this study we identified the human micro RNA hsa-miR-1307-3p as a novel potent suppressor of NS1 expression and influenza virus replication. Transcriptomic analysis indicates that hsa-miR-1307-3p also negatively regulates apoptosis and promotes cell proliferation. In addition, we identified a novel mutation in the NS1 gene of A(H1N1)pdm09 strains circulating in Italy in the 2010-11 season, which enabled the virus to escape the hsa-miR-1307-3p inhibition, conferring replicative advantage to the virus in human cells. To the best of our knowledge, this is the first validation of suppression of IAV H1N1 NS1 by a human micro...
Source: Antiviral Research - August 27, 2019 Category: Virology Authors: Bavagnoli L, Campanini G, Forte M, Ceccotti G, Percivalle E, Bione S, Lisa A, Baldanti F, Maga G Tags: Antiviral Res Source Type: research

Innate immune protection from pneumonia virus of mice induced by a novel immunomodulator is prolonged by dual treatment and mediated by macrophages.
Abstract Respiratory syncytial virus (RSV) is responsible for a large proportion of acute lower respiratory tract infections, specifically in children. Pneumonia virus of mice (PVM) causes similar lung pathology and clinical disease in rodents, and is therefore an appropriate model of RSV infection. Previously, we demonstrated that a single intranasal dose of P-I-P, a novel immunomodulator composed of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene, confers protection in Balb/c mice for up to 3 days from lethal PVM-15 infection. In the present study a dual intr...
Source: Antiviral Research - August 27, 2019 Category: Virology Authors: Martinez EC, Garg R, van Drunen Littel-van den Hurk S Tags: Antiviral Res Source Type: research

Antiviral activity of ST081006 against the Dengue virus.
In this study, we constructed a DENV2-EGFP infectious clone, established a fluorescence-based, high-throughput screening platform, and conducted a screen for anti-DENV compounds on a flavonoid-derivative library, Amongst the hits identified, ST081006 was found to be a strong inhibitor of the DENV replication. Time-course studies suggest that the presence of ST081006 is necessary to inhibit successive rounds of virus replication. Further investigations demonstrated that ST081006 affects the synthesis of both viral protein and viral RNA, and one anti-DENV mechanism is the direct inhibition of viral protein synthesis. The rep...
Source: Antiviral Research - August 14, 2019 Category: Virology Authors: Lee JK, Chui JLM, Lee RCH, Kong HY, Chin WX, Chu JJH Tags: Antiviral Res Source Type: research

Small molecule grp94 inhibitors with antiviral activity against Dengue and Zika virus.
This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications. PMID: 31421166 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - August 14, 2019 Category: Virology Authors: Rothan HA, Zhong Y, Sanborn MA, Teoh TC, Ruan J, Yusof R, Hang J, Henderson MJ, Fang S Tags: Antiviral Res Source Type: research

Efficacy of clarithromycin against H5N1 and H7N9 avian influenza a virus infection in cynomolgus monkeys.
We examined the prophylactic and therapeutic efficacy of CAM against H5N1 highly pathogenic and H7N9 low pathogenic avian influenza virus infections in cynomolgus monkeys. CAM suppressed H5N1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammatory cytokines in the lungs of monkeys infected with H5N1 and H7N9 viruses. The prophylactic administration of CAM showed more suppressive effects on clinical signs of disease and viral titers than did therapeutic administration. Thus, since administration of CAM alone showed a tendency to amel...
Source: Antiviral Research - August 14, 2019 Category: Virology Authors: Arikata M, Itoh Y, Shichinohe S, Nakayama M, Ishigaki H, Kinoshita T, Le MQ, Kawaoka Y, Ogasawara K, Shimizu T Tags: Antiviral Res Source Type: research

FDA-drug screening identifies deptropine inhibiting hepatitis E virus involving the NF- κB-RIPK1-caspase axis.
In this study, we performed a screening of a library containing over 1,000 FDA-approved drugs. We have identified deptropine, a classical histamine H1 receptor antagonist used to treat asthmatic symptoms, as a potent inhibitor of HEV replication. The anti-HEV activity of deptropine appears dispensable of the histamine pathway, but requires the inhibition on nuclear factor-κB (NF-κB) activity. This further activates caspase mediated by receptor-interacting protein kinase 1 (RIPK1) to restrict HEV replication. Given deptropine being widely used in the clinic, our results warrant further evaluation of its anti-HEV...
Source: Antiviral Research - August 12, 2019 Category: Virology Authors: Qu C, Li Y, Li Y, Yu P, Li P, Donkers JM, van de Graaf SF, de Man RA, Peppelenbosch MP, Pan Q Tags: Antiviral Res Source Type: research

Investigation of hepatitis B virus (HBV) rtS78T/sC69* mutation in a large cohort of chronic HBV-infected patients with nucleoside/nucleotide analogue treatment.
This study aimed to investigate clinical occurrence and significance of the rtS78T/sC69* mutation of hepatitis B virus (HBV). A total of 22,009 consecutive chronic HBV-infected patients who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital (Original name Beijing 302 Hospital) from 2007 to 2016 were enrolled. Serum samples were collected for sequence analysis of HBV reverse-transcriptase (RT) and S regions. Phenotypic analysis was performed to evaluate the viral replication capacity and drug susceptibility. The rtS78T mutation was detected in 0.83% (182/22,009) of the patients' samples...
Source: Antiviral Research - August 6, 2019 Category: Virology Authors: Luo D, Liu Y, Chen R, Niu M, Liu L, Li X, Li Q, Huang B, Wang J, Xu D, Lin S Tags: Antiviral Res Source Type: research

Sofosbuvir susceptibility of genotype 1 to 6 HCV from DAA-na ïve subjects.
Sofosbuvir susceptibility of genotype 1 to 6 HCV from DAA-naïve subjects. Antiviral Res. 2019 Aug 05;:104574 Authors: Han B, Martin R, Xu S, Parvangada A, Svarovskaia ES, Mo H, Dvory-Sobol H Abstract High sequence diversity of HCV may lead to variation in susceptibility to antiviral agents amongst different genotypes and subtypes of the virus. We assessed the susceptibility to sofosbuvir of chimeric replicons carrying the full length NS5B coding region from 479 HCV infected, treatment-naïve patients, including 15 subtypes in 6 genotypes. NS5B replicon vectors with subtype 1b, subtype 4a and ...
Source: Antiviral Research - August 5, 2019 Category: Virology Authors: Han B, Martin R, Xu S, Parvangada A, Svarovskaia ES, Mo H, Dvory-Sobol H Tags: Antiviral Res Source Type: research

Yeast-produced subunit protein vaccine elicits broadly neutralizing antibodies that protect mice against Zika virus lethal infection.
Abstract Zika virus (ZIKV) infection is a serious public health concern due to its ability to induce neurological defects and its potential for rapid transmission at a global scale. However, no vaccine is currently available to prevent ZIKV infection. Here, we report the development of a yeast-derived subunit protein vaccine for ZIKV. The envelope protein domain III (EDIII) of ZIKV was produced as a secretory protein in the yeast Pichia pastoris. The yeast-derived EDIII could inhibit ZIKV infection in vitro in a dose-dependent manner, suggesting that it had acquired an appropriate conformation to bind to cellular ...
Source: Antiviral Research - August 5, 2019 Category: Virology Authors: Zhang W, Qu P, Li D, Zhang C, Liu Q, Zou G, Dupont-Rouzeyrol M, Lavillette D, Jin X, Yin F, Huang Z Tags: Antiviral Res Source Type: research

Heterologous protection against Crimean-Congo hemorrhagic fever in mice after a single dose of replicon particle vaccine.
ou CF Abstract No vaccines are currently licensed to prevent Crimean-Congo hemorrhagic fever virus (CCHFV) infection, which can cause mild self-limiting clinical signs or severe, often fatal hemorrhagic fever disease. Here we continued investigations into the utility of a single-dose virus replicon particle (VRP) vaccine regimen by assessing protection against Turkey or Oman strains of CCHFV. We found that all mice were completely protected from disease, supporting broad applicability of this platform for CCHFV prevention. PMID: 31377243 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - August 1, 2019 Category: Virology Authors: Spengler JR, Welch SR, Scholte FEM, Coleman-McCray JD, Harmon JR, Nichol ST, Bergeron É, Spiropoulou CF Tags: Antiviral Res Source Type: research

Aurora kinase A promotes hepatitis B virus replication and expression.
Abstract Cellular protein kinases play critical roles in various steps of the hepatitis B virus life cycle. We found that viral replication in infected or transfected hepatoma cell was markedly inhibited by treatment with A-443654, a specific inhibitor of Akt. The antiviral mechanism of the drug mainly depended on the downregulation of Aurora A, a protein kinase that plays an essential role in mitosis but has not been implicated in the viral life cycle. Our data indicated that Aurora kinase A enhances viral replication and expression independently of its kinase activity required for mitotic function. Our findings ...
Source: Antiviral Research - July 31, 2019 Category: Virology Authors: Jeong GU, Ahn BY Tags: Antiviral Res Source Type: research

An endogenous retroviral element exerts an antiviral innate immune function via the derived lncRNA lnc-ALVE1-AS1.
Abstract Endogenous retroviruses (ERVs) constitute an important component of animal and human genomes and are usually silenced by epigenetic mechanisms in adult cells. Although ERVs were recently reported to be linked to early development, tumorigenesis and autoimmune disease, their impacts on antiviral innate immunity and the underlying mechanisms have not been elucidated. Here, we provide the first direct evidence of an endogenous retroviral element affecting antiviral innate immunity via its derived antisense long non-coding RNA (lncRNA). We found that an antisense lncRNA, which is called lnc-ALVE1-AS1 and is t...
Source: Antiviral Research - July 30, 2019 Category: Virology Authors: Chen S, Hu X, Cui IH, Wu S, Dou C, Liu Y, Sun Z, Xue S, Geng T, Liu Z, Qin A, Cui H Tags: Antiviral Res Source Type: research

Antiviral candidates against the hepatitis E virus (HEV) and their combinations inhibit HEV growth in in vitro.
In this study, we used 27 antiviral compounds, including 15 nucleos(t)ide analogs, for in vitro screening against a genotype 3 HEV strain containing a Gaussia luciferase reporter. RBV, SOF, 2'-C-methyladenosine, 2'-C-methylcytidine (2CMC), 2'-C-methylguanosine (2CMG), and two 4'-azido nucleoside analogs (R-1479 and RO-9187) suppressed replication of the reporter genome, while only RBV, SOF, 2CMC and 2CMG inhibited the growth of genotype 3 HEV in cultured cells. Although 2CMG and RBV (2CMG/RBV) exhibited a synergistic effect while SOF/RBV and 2CMC/RBV showed antagonistic effects on the reporter assay, these three nucleos(t)...
Source: Antiviral Research - July 27, 2019 Category: Virology Authors: Nishiyama T, Kobayashi T, Jirintai S, Nagashima S, Primadharsini PP, Nishizawa T, Okamoto H Tags: Antiviral Res Source Type: research

High-throughput screening for negative-stranded hemorrhagic fever viruses using reverse genetics.
Abstract Viral hemorrhagic fevers (VHFs) cause thousands of fatalities every year, but the treatment options for their management remain very limited. In particular, the development of therapeutic interventions is restricted by the lack of commercial viability of drugs targeting individual VHF agents. This makes approaches like drug repurposing and/or the identification of broad range therapies (i.e. those directed at host responses or common proviral factors) highly attractive. However, the identification of candidates for such antiviral repurposing or of host factors/pathways important for the virus life cycle i...
Source: Antiviral Research - July 26, 2019 Category: Virology Authors: Wendt L, Bostedt L, Hoenen T, Groseth A Tags: Antiviral Res Source Type: research

FoxO4 inhibits HBV core promoter activity through ERK-mediated downregulation of HNF4 α.
FoxO4 inhibits HBV core promoter activity through ERK-mediated downregulation of HNF4α. Antiviral Res. 2019 Jul 25;:104568 Authors: Li L, Li Y, Xiong Z, Shu W, Yang Y, Guo Z, Gao B Abstract Hepatitis B virus (HBV) infection remains a global health problem, causing nearly one million deaths annually. Forkhead box O (FoxO) transcription factors play important roles in modulating diverse physiological processes. Recent studies show that FoxOs are involved in antiviral responses. In present investigation, we found that HBV induced significant down-regulation of FoxO4 protein, while had little effect...
Source: Antiviral Research - July 25, 2019 Category: Virology Authors: Li L, Li Y, Xiong Z, Shu W, Yang Y, Guo Z, Gao B Tags: Antiviral Res Source Type: research

Polyphenylene carboxymethylene (PPCM) in vitro antiviral efficacy against Ebola virus in the context of a sexually transmitted infection.
Abstract Ebola virus disease (EVD) is caused by Ebola virus (EBOV) and characterized in humans by hemorrhagic fever with high fatality rates. Human-to-human EBOV transmission occurs by physical contact with infected body fluids, or indirectly by contaminated surfaces. Sexual transmission is a route of infection only recently documented despite isolating EBOV virus or genome in the semen since 1976. Data on dissemination of EBOV from survivors remain limited and EBOV pathogenesis in humans following sexual transmission is unknown. The in vitro antiviral efficacy of polyphenylene carboxymethylene (PPCM) against EBOV...
Source: Antiviral Research - July 24, 2019 Category: Virology Authors: Escaffre O, Juelich TL, Freiberg AN Tags: Antiviral Res Source Type: research

Responses of human mast cells and epithelial cells following exposure to influenza A virus.
In this study, we characterized and compared the responses of the human mast cell line, LAD2, and human lung epithelial cell line, Calu-3, against three influenza A virus strains; A/PR/8/34 (H1N1), A/WS/33 (H1N1) and A/HK/8/68 (H3N2). We found that there were strain-dependent mast cell responses, and different profiles of cytokine, chemokine and antiviral gene expression between the two cell types. All three strains did not induce histamine or β-hexosaminidase release in LAD2. A/HK/8/68 induced release of prostaglandin D2 in LAD2, whereas A/PR/8/34 and A/WS/33 did not. We found that, among those examined, only CCL4 (b...
Source: Antiviral Research - July 23, 2019 Category: Virology Authors: Ng K, Raheem J, St Laurent CD, Marcet CT, Vliagoftis H, Befus AD, Moon TC Tags: Antiviral Res Source Type: research

Rapid isolation of a potent human antibody against H7N9 influenza virus from an infected patient.
In this study, a neutralizing human antibody named 3L11 was rapidly isolated from the switched memory B cells of a patient infected with H7N9. The antibody 3L11 was encoded by the heavy-chain VH1-8 gene and the light-chain VL2-13 gene that had undergone somatic mutations, and conferred high affinity binding to H7N9 hemagglutinins (HAs). It promoted killing of infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Epitope mapping by mass spectroscopy (MS) indicated that 3L11 bound to the peptide 149-175 of HAs that contained the 150-loop of the receptor-binding site (RBS). Additionally, the 3L11 escape stra...
Source: Antiviral Research - July 20, 2019 Category: Virology Authors: Li J, Yang Y, Wang M, Ren X, Yang Z, Liu L, Zhang G, Chen Q, Yang W, Chen YH, Wan X Tags: Antiviral Res Source Type: research

Susceptibility of Enterovirus-D68 to RNAi-mediated antiviral knockdown.
Abstract Enterovirus D68 (EV-D68) represents an emerging pathogen which has demonstrated a capacity for causing epidemic illness in pediatric and immunocompromised patients. With no effective antiviral treatment available, therapeutic interventions are currently limited to supportive care. Utilizing available genomic sequences from the 2014 B3 Epidemic EV-D68 clade and the 1962 Fermon EV-D68 strains, we performed in silico comparative genomic analysis, identifying several islands of phylogenetic conservation within the viral RNA-dependent RNA polymerase gene. The effects of transfecting short-interfering double-st...
Source: Antiviral Research - July 20, 2019 Category: Virology Authors: Klaiber N, McVoy MA, Zhao W Tags: Antiviral Res Source Type: research

Cat flu: Broad spectrum polymeric antivirals.
In this study, we made an effort to evaluate antiviral potency of poly(sodium 4-styrenesulfonates) (PSSNa) as potent FHV-1 and FCV inhibitors for topical use. Mechanistic studies showed that PSSNa exhibits a different mechanism of action depending on target species. While PSSNa acts directly on FHV-1 particles blocking their interaction with the host's cell and preventing the infection, the antiviral potency against FCV is based on inhibition at late stages of the viral replication cycle. Altogether, PSSNa polymers are promising drug candidates to be used in the treatment and prevention of the viral upper respiratory tract...
Source: Antiviral Research - July 17, 2019 Category: Virology Authors: Synowiec A, Gryniuk I, Pachota M, Strzelec Ł, Roman O, Kłysik-Trzciańska K, Zając M, Drebot I, Gula K, Andruchowicz A, Rajfur Z, Szczubiałka K, Nowakowska M, Pyrc K Tags: Antiviral Res Source Type: research

New antibody-based prevention and treatment options for influenza.
Abstract The antigenic diversity of human influenza viruses represents a challenge to the development of vaccines with durable immune protection. In addition, small molecule anti-influenza viral drugs can bring clinical relief to influenza patients but the emergence of drug resistant viruses can rapidly limit the effectiveness of such drugs. In the past decade, a number of human monoclonal antibodies have been described that can bind to and neutralize a broad range of influenza A and B viruses. Most of these monoclonal antibodies are directed against the viral hemagglutinin (HA) stalk and some have now been evalua...
Source: Antiviral Research - July 16, 2019 Category: Virology Authors: Sedeyn K, Saelens X Tags: Antiviral Res Source Type: research

The Val430Ile neuraminidase (NA) substitution, identified in influenza B virus isolates, impacts the catalytic 116Arg residue causing reduced susceptibility to NA inhibitors.
Abstract As part of a 2015-2018 clinical trial of peramivir treatment for acute influenza infections in the elderly, an influenza B/Yamagata/16/1988-like isolate harbouring a Val430Ile neuraminidase (NA) substitution was recovered from a single patient. This substitution was detected in respiratory samples collected before and during peramivir treatment. In NA inhibition assays, oseltamivir, zanamivir and peramivir IC50s of the Val430Ile isolate were 4-, 15- and 16-fold higher compared to a wild-type (WT) strain. In reverse genetics experiments, the Ile430Val reversion restored the drug susceptible phenotype. The ...
Source: Antiviral Research - July 16, 2019 Category: Virology Authors: Abed Y, Fage C, Checkmahomed L, Begin G, Carbonneau J, Lague P, Boivin G Tags: Antiviral Res Source Type: research

NVN1000, a novel nitric oxide-releasing compound, inhibits HPV-18 virus production by interfering with E6 and E7 oncoprotein functions.
PMID: 31319090 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - July 15, 2019 Category: Virology Authors: Banerjee NS, Moore DW, Wang HK, Broker TR, Chow LT Tags: Antiviral Res Source Type: research

Intraperitoneal injection with dengue virus type 1-infected K562  cells results in complete fatality among immunocompetent mice.
Intraperitoneal injection with dengue virus type 1-infected K562 cells results in complete fatality among immunocompetent mice. Antiviral Res. 2019 Jul 13;:104560 Authors: Yamanaka A, Konishi E Abstract Dengue is one of the most important mosquito-borne viral diseases. Over half of the world's population is living in dengue endemic countries, where 100 million cases are estimated to occur annually. Although one dengue vaccine is currently available commercially, unfortunately its safety and efficacy has not been demonstrated for seronegative populations. Therefore, other vaccine candidates as well a...
Source: Antiviral Research - July 13, 2019 Category: Virology Authors: Yamanaka A, Konishi E Tags: Antiviral Res Source Type: research

Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus.
Iminosugars counteract the downregulation of the interferon γ receptor by dengue virus. Antiviral Res. 2019 Jul 12;:104551 Authors: Miller JL, Hill ML, Brun J, Pountain A, Sayce AC, Zitzmann N Abstract The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum α-glucosidase enzymes. Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo. We investigated...
Source: Antiviral Research - July 12, 2019 Category: Virology Authors: Miller JL, Hill ML, Brun J, Pountain A, Sayce AC, Zitzmann N Tags: Antiviral Res Source Type: research

Meeting report: 32nd International Conference on Antiviral Research.
This report gives an overview of the conference on behalf of the Society. It provides a general review of the meeting and awardees, summarizing the presentations, and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. As in past years, ICAR promoted and showcased the most recent progress in antiviral research, and continued to foster collaborations and interactions in drug discovery and development. The 33rd ICAR will be held in Seattle, Washington, USA, March 30th-April 3rd, 2020. PMID: 31302149 [PubMed - as supplied by publisher] (Source: Antiviral Research)
Source: Antiviral Research - July 11, 2019 Category: Virology Authors: Tramontano E, Tarbet B, Spengler JR, Seley-Radtke K, Meier C, Jordan R, Janeba Z, Gowen B, Gentry B, Esté JA, Bray M, Andrei G, Schang LM, International Society for Antiviral Research Tags: Antiviral Res Source Type: research

The ReFRAME library as a comprehensive drug repurposing library to identify mammarenavirus inhibitors.
Abstract Several mammarenaviruses, chiefly Lassa virus (LASV) in Western Africa and Junín virus (JUNV) in the Argentine Pampas, cause severe disease in humans and pose important public health problems in their endemic regions. Moreover, mounting evidence indicates that the worldwide-distributed mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. The lack of licensed mammarenavirus vaccines and partial efficacy of current anti-mammarenavirus therapy limited to an off-label use of the nucleoside analog ribavirin underscore an unmet need for novel th...
Source: Antiviral Research - July 11, 2019 Category: Virology Authors: Kim YJ, Cubitt B, Chen E, Hull MV, Chatterjee AK, Cai Y, Kuhn JH, de la Torre JC Tags: Antiviral Res Source Type: research

BAY 41-4109-mediated aggregation of assembled and misassembled HBV capsids in cells revealed by electron microscopy.
Abstract HBc is a small protein essential for the formation of the icosahedral HBV capsid. Its multiple roles in the replication cycle make this protein a promising target for the development of antiviral molecules. Based on the structure of HBc, a series of HBV assembly inhibitors, also known as capsid assembly modulators, were identified. We investigated the effect of BAY 41-4109, a heteroaryldihydropyrimidine derivative that promotes the assembly of a non-capsid polymer. We showed, by confocal microscopy, that BAY 41-4109 mediated HBc aggregation, mostly in the cytoplasm of Huh7 cells. Image analysis revealed t...
Source: Antiviral Research - July 11, 2019 Category: Virology Authors: Rat V, Seigneuret F, Burlaud-Gaillard J, Lemoine R, Hourioux C, Zoulim F, Testoni B, Meunier JC, Tauber C, Roingeard P, de Rocquigny H Tags: Antiviral Res Source Type: research

A cross-reactive human monoclonal antibody targets the conserved H7 antigenic site a from fifth wave H7N9-infected humans.
Abstract Subtype H7 avian influenza viruses have been found to be associated with human infection and represent a risk for global public health. In 2013, the emergence of H7N9 virus in human beings and persistent human infection in China raised the most serious pandemic threat. Here we identified a human monoclonal antibody, P52E03, targeting the hemagglutinin (HA) of subtype H7 influenza viruses (H7 antigen), from a convalescent patient infected with H7N9 in 2017. P52E03 showed in vitro hemagglutination inhibiting (HI) and neutralizing activity against subtype H7 viruses belonging to both North American and Euras...
Source: Antiviral Research - July 9, 2019 Category: Virology Authors: Li M, Chen L, Wang Q, Hao M, Zhang X, Liu L, Yu X, Yang C, Xu J, Chen J, Gong R Tags: Antiviral Res Source Type: research

Dual effects of the novel ingenol derivatives on the acute and latent HIV-1 infections.
Abstract The latent reservoir of HIV-1 in resting memory CD4+ T cells serves as a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 is proposed as a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current latency reversal agents (LRAs), identification of new LRAs is urgently required. Here, we analyzed Euphorbia kansui extracts and obtained three ingenol derivative compounds named EK-1A, EK-5A and EK-15A. We found that ingenol derivatives can effectively reactivate latent HIV-1 at very low (nanomolar) concentrations in HIV latency model in vitro. Furt...
Source: Antiviral Research - July 8, 2019 Category: Virology Authors: Yang H, Li X, Yang X, Lu P, Wang Y, Jiang Z, Pan H, Zhao L, Zhu Y, Khan I, Shen Y, Lu H, Zhang T, Jiang G, Ma Z, Wu H, Zhu H Tags: Antiviral Res Source Type: research