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Antiviral Research

Toni L Meister, Janina Bruening, Daniel Todt, Eike Steinmann
Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and is the leading cause of enterically-transmitted viral hepatitis worldwide. Increasing numbers of HEV infections, together with no available specific anti-HEV treatment, contributes to the pathogen's major health burden. A robust cell culture system is required for virologic studies and the development of new antiviral drugs. Unfortunately, like other hepatitis viruses, HEV is difficult to propagate in conventional cell lines. Many different cell culture systems have been tested using various HEV strains, but viral replication usually progresses very slowly, and infection with low virion counts results in non-productive HEV replication...
January 14, 2019: Antiviral Research
Rachele Francese, Andrea Civra, Massimo Rittà, Manuela Donalisio, Monica Argenziano, Roberta Cavalli, Ali S Mougharbel, Ulrich Kortz, David Lembo
Zika virus (ZIKV) is an emerging infectious viral pathogen associated with severe fetal cerebral anomalies and the paralytic Guillain-Barrè syndrome in adults. It was the cause of a recent global health crisis following its entrance into a naïve population in the Americas. Nowadays, no vaccine or specific antiviral against ZIKV is available. In this study, we identified three polyoxometales (POMs), the Anderson-Evans type [TeW6 O24 ]6- (TeW6 ), and the Keggin-type [TiW11 CoO40 ]8- _ (TiW11 Co), and [Ti2 PW10 O40 ]7- (Ti2 PW10 ), that inhibit ZIKV infection with EC50 s in the low micromolar range...
January 14, 2019: Antiviral Research
Ana S Ferreira-Ramos, Changqing Li, Cécilia Eydoux, Jean Marie Contreras, Christophe Morice, Gilles Quérat, Alba Gigante, María-Jesús Pérez Pérez, Marie-Louise Jung, Bruno Canard, Jean-Claude Guillemot, Etienne Decroly, Bruno Coutard
Alphaviruses such as the Venezuelan equine encephalitis virus (VEEV) are important human emerging pathogens transmitted by mosquitoes. They possess a unique viral mRNA capping mechanism catalyzed by the viral non-structural protein nsP1, which is essential for virus replication. The alphaviruses capping starts by the methylation of a GTP molecule by the N7-guanine methyltransferase (MTase) activity; nsP1 then forms a covalent link with m7 GMP releasing pyrophosphate (GT reaction) and the m7 GMP is next transferred onto the 5'-diphosphate end of the viral mRNA to form a cap-0 structure...
January 10, 2019: Antiviral Research
Mehrangiz Dezhbord, Sooyoung Lee, Woohyun Kim, Baik Lin Seong, Wang-Shick Ryu
Despite the utmost importance of cccDNA in HBV biology, the mechanism by which cccDNA synthesis is regulated is not completely understood. Here we explored HepG2-NTCP cell line and performed a time-course HBV infection experiment (up to 30 days) to follow the conversion of the input viral DNA into cccDNA. We found that a protein-free RC DNA (PF-RC DNA) become detectable as early as 12 h post infection (hpi) prior to the detection of cccDNA, which become evident only at 2-3 dpi. Intriguingly, the PF-RC DNA detected at 12 hpi was abundantly located in the cytoplasm, implicating that the protein-removal from the input viral DNA takes place in the cytoplasm, perhaps inside the nucleocapsid...
January 10, 2019: Antiviral Research
Myung Hee Kim, Jung-Ok Kang, Joo-Young Kim, Hi Eun Jung, Heung Kyu Lee, Jun Chang
Nucleoprotein is highly conserved among each type of influenza viruses (A and B) and has received significant attention as a good target for universal influenza vaccine. In this study, we determined whether a recombinant adenovirus encoding nucleoprotein of type B influenza virus (rAd/B-NP) confers protection against influenza virus infection in mice. We also identified a cytotoxic T lymphocyte epitope in the nucleoprotein to determine B-NP-specific CD8 T-cell responses. We found that B-NP-specific CD8 T cells induced by rAd/B-NP immunization played a major role in protection following influenza B virus infection using CD8 knockout mice...
January 9, 2019: Antiviral Research
Phuc H Pham, Bibi S H Sokeechand, Mark Evan Hamilton, Ehab Misk, Ginny Jones, Lucy E J Lee, John S Lumsden, Niels C Bols
The heat-shock protein 70 (Hsp70) inhibitor, VER-155008 (VER), was explored as a potential antiviral agent for two RNA viruses important to fish aquaculture, viral hemorrhagic septicemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV). Studies were done at a temperature of 14 °C, and with cell lines commonly used to propagate these viruses. These were respectively EPC from fathead minnow for VHSV and CHSE-214 from Chinook salmon embryo for IPNV. Additionally, both viruses were studied with the Atlantic salmon heart endothelial cell line ASHe...
January 6, 2019: Antiviral Research
Cheng-Hsun Ho, Shu-Hui Chen, Hung-Wen Tsai, I-Chin Wu, Ting-Tsung Chang
N-glycosylation on the crystallizable fragment (Fc) governs antibody-mediated immune responses. This study addressed the relevance of N-acetylglucosamine (GlcNAc)-bisected IgG1 on the disease progression and treatment efficacy in the immune active phase of chronic hepatitis B virus (HBV) infection. Serum IgG1 N-glycan patterns from 166 HBV e antigen (HBeAg)-positive patients were analyzed using liquid chromatography-tandem mass spectrometry. The proportion of GlcNAc-bisected IgG1 on the disease severity and efficacy of nucleos(t)ide analogue treatment were investigated...
January 3, 2019: Antiviral Research
Meir Kende, Jason Paragas, Andres M Salazar
The potential protection of poly-ICLC (Hiltonol® ) a double stranded RNA (dsRNA) against EZV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EZV serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine Ebola virus challenge models, when treatment is started on the day of -or one day after virus challenge...
January 3, 2019: Antiviral Research
Gerson Dierley Keppeke, S John Calise, Edward K L Chan, Luis Eduardo C Andrade
Ribavirin (RBV) is a guanosine analogue triazole most commonly used in the treatment of chronic hepatitis C (HCV) infection. Although its mechanism of action is a matter of debate, several possibilities have been proposed, including depletion of guanine nucleotides through inhibition of inosine monophosphate dehydrogenase (IMPDH). IMPDH has been shown to assemble into micron-scale rod- and ring-shaped structures (rods/rings or RR), also called "IMPDH filaments," both in vitro and in vivo. Formation of RR structures can occur naturally, potentially to influence IMPDH activity, or when de novo guanosine monophosphate biosynthesis or IMPDH itself are inhibited by nutrient deprivation or drugs like RBV...
December 31, 2018: Antiviral Research
Cheng Li, Yang Wang, Tiantian Liu, Matthias Niklasch, Ke Qiao, Sarah Durand, Li Chen, Mifang Liang, Thomas F Baumert, Shuping Tong, Michael Nassal, Yu-Mei Wen, Yong-Xiang Wang
Hepatitis B virus (HBV) envelopes as well as empty subviral particles carry in their lipid membranes the small (S), middle (M), and large (L) surface proteins, collectively known as hepatitis B surface antigen (HBsAg). Due to their common S domain all three proteins share a surface-exposed hydrophilic antigenic loop (AGL) with a complex disulfide bridge-dependent structure. The AGL is critical for HBV infectivity and virion secretion, and thus represents a major target for neutralizing antibodies. Previously, a human monoclonal antibody (mAb) targeting a conformational epitope in the AGL, IgG12, exhibited 1000-fold higher neutralizing activity than hepatitis B immune globulin (HBIG)...
December 30, 2018: Antiviral Research
Laurent Mailly, Florian Wrensch, Laura Heydmann, Catherine Fauvelle, Nicolas Brignon, Mirjam B Zeisel, Patrick Pessaux, Zhen-Yong Keck, Catherine Schuster, Thomas R Fuerst, Steven K H Foung, Thomas F Baumert
Despite the development of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection remains a major cause for liver disease and cancer worldwide. Entry inhibitors block virus host cell entry and, therefore, prevent establishment of chronic infection and liver disease. Due to their unique mechanism of action, entry inhibitors provide an attractive antiviral strategy in organ transplantation. In this study, we developed an innovative approach in preventing HCV infection using a synergistic combination of a broadly neutralizing human monoclonal antibody (HMAb) targeting the HCV E2 protein and a host-targeting anti-claudin 1 (CLDN1) humanized monoclonal antibody...
December 29, 2018: Antiviral Research
Athanase Badolo, Felicity Burt, Susan Daniel, Rachel Fearns, Eduardo Samo Gudo, Margaret Kielian, Julien Lescar, Yi Shi, Albrecht von Brunn, Susan R Weiss, Rolf Hilgenfeld
The Third Tofo Advanced Study Week on Emerging and Re-Emerging Viruses (3rd TASW) was held in Praia do Tofo, Mozambique, from September 02 to 06, 2018. It brought together 55 participants from 9 African countries as well as from Belgium, China, Germany, Singapore, and the USA. Meeting sessions covered aspects of the epidemiology, diagnosis, molecular and structural biology, vaccine development, and antiviral drug discovery for emerging RNA viruses that are current threats in Africa and included flaviviruses (dengue and Zika), alphaviruses (chikungunya), coronaviruses, filoviruses (Ebola), influenza viruses, Crimean Congo hemorrhagic fever virus, Rift Valley fever Virus, Lassa virus, and others...
December 28, 2018: Antiviral Research
Siew Pheng Lim
In the context of the only available vaccine (DENGVAXIA) that was marketed in several countries, but poses higher risks to unexposed individuals, the development of antivirals for dengue virus (DENV), whilst challenging, would bring significant benefits to public health. Here recent progress in the field of DENV drug discovery made in academic laboratories and industry is reviewed. Characteristics of an ideal DENV antiviral molecule, given the specific immunopathology provoked by this acute viral infection, are first described...
December 28, 2018: Antiviral Research
Enrique Bernal, Mónica Martinez, Ana Torres, Concepción F Guillamón, Antonia Alcaraz, María J Alcaraz, Angeles Muñoz, Salvador Valero, Carmen Botella, José A Campillo, Alfredo Cano, Alfredo Minguela
The main objective of this study is to evaluate the predictive capacity of T cell activation/senescence in subclinical atherosclerosis (SCA) in a group of HIV-infected patients. So, an observational and longitudinal study was performed on 91 long-term triple-ART therapy HIV-infected patients. Carotid Intima Media Thickness (cIMT) was measured. Binary logistic regression was used to evaluate independent variables associated with SCA. Compared to patients without SCA, patients with SCA (60.4%) were older (41...
December 26, 2018: Antiviral Research
Stuart Le Grice, Elias Maccioni, Angela Corona, Cristina Parolin, Enzo Tramontano
The 4th Summer School on Innovative Approaches for the Identification of Antiviral Agents (IAAASS) was held at the Sardegna Ricerche Research Park in Santa Margherita di Pula, Sardinia, Italy from September 24-28, 2018. The Summer School assembled 21 internationally recognized experts and 46 graduate and postgraduate students, with the goal of discussing advances in antiviral drug discovery from the perspective of high-throughput screening, medicinal chemistry, computational chemistry, virology, molecular and structural biology...
December 23, 2018: Antiviral Research
Tomomi Shiroishi-Wakatsuki, Masami Maejima-Kitagawa, Akiko Hamano, Daigo Murata, Sayaka Sukegawa, Kazuhiro Matsuoka, Hirotaka Ode, Atsuko Hachiya, Mayumi Imahashi, Yoshiyuki Yokomaku, Nobuhiko Nomura, Wataru Sugiura, Yasumasa Iwatani
Antiretroviral therapy (ART) against HIV-1 infection offers the promise of controlling disease progression and prolonging the survival of HIV-1-infected patients. However, even the most potent ART regimens available today cannot cure HIV-1. Because patients will be exposed to ART for many years, physicians and researchers must anticipate the emergence of drug-resistant HIV-1, potential adverse effects of the current drugs, and need for future drug development. In this study, we screened a small-molecule compound library using cell-based anti-HIV-1 assays and discovered a series of novel anti-HIV-1 compounds, 4-oxoquinolines...
December 21, 2018: Antiviral Research
Manunya Nuth, Hancheng Guan, Yuhong Xiao, John L Kulp, Michael H Parker, Eric D Strobel, Stuart N Isaacs, Richard W Scott, Allen B Reitz, Robert P Ricciardi
The smallpox virus (variola) remains a bioterrorism threat since a majority of the human population has never been vaccinated. In the event of an outbreak, at least two drugs against different targets of variola are critical to circumvent potential viral mutants that acquire resistance. Vaccinia virus (VACV) is the model virus used in the laboratory for studying smallpox. The VACV processivity factor D4 is an ideal therapeutic target since it is both essential and specific for poxvirus replication. Recently, we identified a tripeptide (Gly-Phe-Ile) motif at the C-terminus of D4 that is conserved among poxviruses and is necessary for maintaining protein function...
December 19, 2018: Antiviral Research
Magali Saez-Ayala, Elsie Laban Yekwa, Clémence Mondielli, Loic Roux, Sergio Hernández, Fabrice Bailly, Philippe Cotelle, Dominga Rogolino, Bruno Canard, François Ferron, Karine Alvarez
Arenaviridae is a viral family whose members are associated with rodent-transmitted infections to humans responsible of severe diseases. The current lack of a vaccine and limited therapeutic options make the development of efficacious drugs of high priority. The cap-snatching mechanism of transcription of Arenavirus performed by the endonuclease domain of the L-protein is unique and essential, so we developed a drug design program targeting the endonuclease activity of the prototypic Lymphocytic ChorioMeningitis Virus...
December 14, 2018: Antiviral Research
R Garg, L Latimer, S Gomis, V Gerdts, A Potter, S van Drunen Littel-van den Hurk
Human parainfluenza virus 3 (PIV3) and respiratory syncytial virus (RSV) are major causative agents of serious respiratory tract illness in newborns and infants. Maternal vaccination could be a promising approach to provide immediate protection against severe PIV3 and RSV infection in young infants. Previously, we demonstrated that maternal immunization with a subunit vaccine consisting of the RSV fusion (F) protein formulated with TriAdj, an adjuvant consisting of poly(I:C), immune defense regulatory peptide and polyphosphazene, protects newborn lambs from RSV...
December 12, 2018: Antiviral Research
Christopher F Basler, Nevan J Krogan, Daisy W Leung, Gaya K Amarasinghe
Filoviruses, which include Ebola virus (EBOV) and Marburg virus, are negative-sense RNA viruses associated with sporadic outbreaks of severe viral hemorrhagic fever characterized by uncontrolled virus replication. The extreme virulence and emerging nature of these zoonotic pathogens make them a significant threat to human health. Replication of the filovirus genome and production of viral RNAs require the function of a complex of four viral proteins, the nucleoprotein (NP), viral protein 35 (VP35), viral protein 30 (VP30) and large protein (L)...
December 11, 2018: Antiviral Research
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