Methyl-β-cyclodextrin inhibits EV-D68 virus entry by perturbing the accumulation of virus particles and ICAM-5 in lipid rafts
Publication date: Available online 23 February 2020Source: Antiviral ResearchAuthor(s): Yunhe Jiang, Shunan Liu, Siyu Shen, Haoran Guo, Honglan Huang, Wei WeiAbstractEnterovirus D68 (EV-D68) is a member of the Picornavirus family and a causative agent of respiratory diseases in children. The incidence of EV-D68 infection has increased worldwide in recent years. Thus far, there are no approved antiviral agents or vaccines for EV-D68. Here, we show that methyl-β-cyclodextrin (MβCD), a common drug that disrupts lipid rafts, specifically inhibits EV-D68 infection without producing significant cytotoxicity at virucidal concen...
Source: Antiviral Therapy - February 23, 2020 Category: Virology Source Type: research

Influenza virus NS1- C/EBPβ gene regulatory complex inhibits RIG-I transcription
Publication date: Available online 21 February 2020Source: Antiviral ResearchAuthor(s): Rashmi Kumari, Zhu Guo, Amrita Kumar, Mayim Wiens, Shivaprakash Gangappa, Jacqueline M. Katz, Nancy J. Cox, Renu B. Lal, Devanand Sarkar, Paul B. Fisher, Adolfo García-Sastre, Takashi Fujita, Vijay Kumar, Suryaprakash Sambhara, Priya Ranjan, Sunil K. LalAbstractInfluenza virus non-structural protein 1 (NS1) counteracts host antiviral innate immune responses by inhibiting Retinoic acid inducible gene-I (RIG-I) activation. However, whether NS1 also specifically regulates RIG-I transcription is unknown. Here, we identify a CCAAT/Enhancer ...
Source: Antiviral Therapy - February 23, 2020 Category: Virology Source Type: research

Prophylaxis of ferrets with nitazoxanide and oseltamivir combinations is more effective at reducing the impact of influenza a virus infection compared to oseltamivir monotherapy
In this study we used oseltamivir (OST), a neuraminidase inhibitor and nitazoxanide (NTZ), a host directed drug, and found in vitro that the combination of these two antivirals have a synergistic relationship. Using the ferret model of (A/Perth/265/2009, (H1N1)pdm09), virus infections, we found that the combination of NTZ and OST was more effective than either NTZ or OST independently in preventing infection and reducing duration of viral shedding. However, these benefits were only seen if treatment was administered prophylactically, as opposed to therapeutically. We also found that if prophylactically treated ferrets that...
Source: Antiviral Therapy - February 22, 2020 Category: Virology Source Type: research

Sex-determining region Y box 4 (SOX4) suppresses Hepatitis B virus replication by inhibiting hepatocyte nuclear factor 4α expression
Publication date: Available online 18 February 2020Source: Antiviral ResearchAuthor(s): Shu Shi, Mingchen Liu, Jingyuan Xi, Hui Liu, Guiwen Guan, Congle Shen, Zhengyang Guo, Ting Zhang, Qiang Xu, Dilidaer kudereti, Xiangmei Chen, Jie Wang, Fengmin LuAbstractHepatitis B virus (HBV) infection is still a health care crisis in the world, and a considerable number of chronic hepatitis B patients die of end-stage liver diseases, including liver cirrhosis and hepatocellular carcinoma. A previous study has reported that sex-determining region Y box 4 (SOX4) promotes HBV replication by binding to the AACAAAG motif in the viral geno...
Source: Antiviral Therapy - February 20, 2020 Category: Virology Source Type: research

7-Deaza-7-fluoro modification confers on 4′-cyano-nucleosides potent activity against entecavir/adefovir-resistant HBV variants and favorable safety
Publication date: Available online 18 February 2020Source: Antiviral ResearchAuthor(s): Sanae Hayashi, Nobuyo Higashi-Kuwata, Debananda Das, Kota Tomaya, Kohei Yamada, Shuko Murakami, David J. Venzon, Shin-ichiro Hattori, Masanori Isogawa, Stefan G. Sarafianos, Hiroaki Mitsuya, Yasuhito TanakaAbstractWe designed, synthesized and identified a novel nucleoside derivative, 4′-C-cyano-7-deaza-7-fluoro-2′-deoxyadenosine (CdFA), which exerts potent anti-HBV activity (IC50 ∼26 nM) with favorable hepatocytotoxicity (CC50 ∼56 μM). Southern blot analysis using wild-type HBV (HBVWT)-encoding-plasmid-transfected HepG2 cel...
Source: Antiviral Therapy - February 20, 2020 Category: Virology Source Type: research

Adoptive T-cell therapy for HBV-associated HCC and HBV infection
Publication date: Available online 19 February 2020Source: Antiviral ResearchAuthor(s): Anthony T. Tan, Sophia SchreiberAbstractChronic hepatitis B virus (HBV) infection remains a major global concern due to its high prevalence and the increased probability of progressing toward cirrhosis and hepatocellular carcinoma (HCC). While currently available therapies are effective in controlling HBV replication, they rarely achieve functional cure. Similarly, effective treatment options for HBV-related HCC (HBV-HCC) are limited and primarily applicable only for early stages of the disease. With the general success of chimeric anti...
Source: Antiviral Therapy - February 20, 2020 Category: Virology Source Type: research

Design of TLR2-ligand-synthetic long peptide conjugates for therapeutic vaccination of chronic HBV patients
Publication date: Available online 17 February 2020Source: Antiviral ResearchAuthor(s): Yingying Dou, Diahann T.S.L. Jansen, Aniek van den Bosch, Robert A. de Man, Nadine van Montfoort, Can Araman, Sander I. van Kasteren, Gijs G. Zom, Willem-Jan Krebber, Cornelis J.M. Melief, Andrea M. Woltman, Sonja I. BuschowAbstractSynthetic long peptide (SLP) vaccination is a promising new treatment strategy for patients with a chronic hepatitis B virus (HBV) infection. We have previously shown that a prototype HBV-core protein derived SLP was capable of boosting CD4+ and CD8+ T cell responses in the presence of a TLR2-ligand in chroni...
Source: Antiviral Therapy - February 18, 2020 Category: Virology Source Type: research

The direct and indirect consequences of cytomegalovirus infection and potential benefits of vaccination
This article describes the studies that have been conducted to date and emphasises that mortality after stem cell transplant (not attributed to CMV end-organ disease) has recently become the first proven indirect effect of CMV now that letermovir has significantly reduced non-relapse deaths.The implications for CMV vaccines are then discussed. Vaccines are already predicted to be highly cost-effective if they can reduce CMV end-organ disease. Health planners should now consider that cost effectiveness is likely to be enhanced further through reduction of the indirect effects of CMV. A prototype scheme for assessing this po...
Source: Antiviral Therapy - February 18, 2020 Category: Virology Source Type: research

Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model. (Source: Antiviral Therapy)
Source: Antiviral Therapy - February 18, 2020 Category: Virology Source Type: research

Meeting report: Eleventh international conference on hantaviruses
Publication date: Available online 15 February 2020Source: Antiviral ResearchAuthor(s): Jan Clement, Clas Ahlm, Tatjana Avšič-Županc, Jason Botten, Kartik Chandran, Colleen B. Jonsson, Hiroaki Kariwa, Jonas Klingström, Boris Klempa, Detlev H. Krüger, Herwig Leirs, Dexin Li, Mifang Liang, Alemka Markotić, Anna Papa, Connie S. Schmaljohn, Nicole D. Tischler, Rainer G. Ulrich, Antti Vaheri, Cecilia VialAbstractThe 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1–4, 2019, at the Irish College, in Leuven, Belgium. The...
Source: Antiviral Therapy - February 16, 2020 Category: Virology Source Type: research

Mark Prichard: Scholar, family man and friend
This article pays tribute to Mark as a scholar, family man and friend. (Source: Antiviral Therapy)
Source: Antiviral Therapy - February 14, 2020 Category: Virology Source Type: research

MDA5 against enteric viruses through induction of interferon-like response partially via the JAK-STAT cascade
In this study, we investigated the effects and mode-of-action of MDA5 on the infection of enteric viruses. We found that MDA5 potently inhibited HEV, HuNV and rotavirus replication in multiple cell models. Overexpression of MDA5 induced transcription of important antiviral ISGs through IFN-like response, without triggering of functional IFN production. Interestingly, MDA5 activates the expression and phosphorylation of STAT1, which is a central component of the JAK-STAT cascade and a hallmark of antiviral IFN response. However, genetic silencing of STAT1 or pharmacological inhibition of the JAK-STAT cascade only partially ...
Source: Antiviral Therapy - February 11, 2020 Category: Virology Source Type: research

Long-chain fatty acyl-coenzyme A suppresses hepatitis C virus infection by targeting virion-bound lipoproteins
In this study, we identified the antiviral effects of long-chain fatty acyl-coenzyme A (LCFA-CoA) against the infections of HCV genotypes 1–6 through targeting mature HCV-bound lipoproteins, suggesting novel mechanism(s) of antiviral different from those used by host-targeting agents or DAAs. We found that the antiviral activity of LCFA-CoA relied on the long-chain saturated fatty acid and the CoA group, and was enhanced when combined with pegylated-interferon or DAAs. Importantly, we demonstrated that LCFA-CoA efficiently inhibited the infection of HCV variants carrying DAA-resistant mutations. The mechanistic study rev...
Source: Antiviral Therapy - February 11, 2020 Category: Virology Source Type: research

The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
Publication date: Available online 10 February 2020Source: Antiviral ResearchAuthor(s): B. Coutard, C. Valle, X. de Lamballerie, B. Canard, N.G. Seidah, E. DecrolyAbstractIn 2019, a new coronavirus (2019-nCoV) infecting Humans has emerged in Wuhan, China. Its genome has been sequenced and the genomic information promptly released. Despite a high similarity with the genome sequence of SARS-CoV and SARS-like CoVs, we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs. In this article, we discuss the possible functional consequences of this cleavage site i...
Source: Antiviral Therapy - February 11, 2020 Category: Virology Source Type: research

Prevention and treatment of neonatal herpes simplex virus infection
Publication date: Available online 7 February 2020Source: Antiviral ResearchAuthor(s): Nicole L. Samies, Scott H. JamesAbstractHerpes simplex virus (HSV), a member of the Herpesviridae family, is a well-known cause of infections including genital herpes and herpes labialis in the adolescent and adult population. Transmission of HSV infection to an infant during the first 4–6 weeks of life can lead to devastating disease with the potential for poor outcomes. Early diagnosis is imperative when evaluating neonatal HSV infection in order to prevent further disease progression, neurological complications, and even death. In t...
Source: Antiviral Therapy - February 8, 2020 Category: Virology Source Type: research