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Antiviral Research

T Schräder, S E Dudek, A Schreiber, C Ehrhardt, O Planz, S Ludwig
Influenza A virus (IAV) infections are still a major global threat for humans, especially for the risk groups of young children and the elderly. Annual epidemics and sporadically occurring pandemics highlight the necessity of effective antivirals that can limit viral replication. The currently licensed antiviral drugs target viral factors and are prone to provoke viral resistance. In infected host cells IAV induces various cellular signaling cascades. The Raf/MEK/ERK signaling cascade is indispensable for IAV replication because it triggers the nuclear export of newly assembled viral ribonucleoproteins (vRNPs)...
July 7, 2018: Antiviral Research
Tiago Fazolo, Rodrigo Benedetti Gassen, Deise Nascimento de Freitas, Thiago J Borges, Maurício Menegatti Rigo, Rodrigo Dornelles da Silva, Fábio Maito, Aline Cunha, Daniel Augusto Gasparin Bueno Mendes, André Báfica, José Eduardo Vargas, Ana Paula Duarte de Souza, Cristina Bonorino
Respiratory syncytial virus (RSV) is the most common etiologic agent in severe infections of the lower respiratory tract in children with a high mortality rate. However, there are still no licensed vaccines for RSV. In this study, we investigated a putative vaccine based on M209-223 peptide. Mice vaccinated with M209-223 peptide expanded M209-223 -specific effector CD4+ T cells upon infection. Vaccination resulted in increased numbers of regulatory T cells (Treg) and Th1 cells, and decreased numbers of Th2 cells...
July 7, 2018: Antiviral Research
Lindsay Lundberg, Ashwini Brahms, Idris Hooper, Brian Carey, Shih-Chao Lin, Bibha Dahal, Aarthi Narayanan, Kylene Kehn-Hall
The New World alphaviruses -Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV respectively) - cause a febrile disease that is often lethal in equines and children and leads to long-term neurological sequelae in survivors. Endemic to the Americas, epizootic outbreaks of the three viruses occur sporadically in the continental United States. All three viruses aerosolize readily, replicate to high titers in cell culture, and have low infectious doses. Additionally, there are no FDA-approved vaccines or therapeutics for human use...
July 5, 2018: Antiviral Research
Adam Schafer, Han Cheng, Rui Xiong, Veronica Soloveva, Cary Retterer, Feiyan Mo, Sina Bavari, Gregory Thatcher, Lijun Rong
Ebola and Marburg are filoviruses and biosafety level 4 pathogens responsible for causing severe hemorrhagic fevers in humans with mortality rates up to 90%. The most recent outbreak in West Africa resulted in approximately 11,310 deaths in 28,616 reported cases. Currently there are no FDA-approved vaccines or therapeutics to treat infections of these deadly viruses. Recently we screened an FDA-approved drug library and identified numerous G protein-coupled receptor (GPCR) antagonists including antihistamines possessing anti-filovirus properties...
July 4, 2018: Antiviral Research
Adriana Sierra González, Ana Luiza Guimarães Assmann, Celso Raul Romero Ramos, Miryam Marroquin Quelopana, Aline Carolina Aleixo Silva, Vanete Thomaz-Soccol
To achieve the goal of performing quality control on vaccines for foot-and-mouth disease several steps were performed in this study. First, the gene that encodes the 3ABC region of the A24 Cruzeiro strain (which is used in vaccine production) was amplified. Second, to improve protein stability, the 3ABC protein was mutated at the 3Cpro catalytic site and cloned the amplification products in the pET-SUMO expression vector. In the third step, the resulting recombinant protein was tested, which the polyclonal antibody recognized, with the semi-purified viral 3ABC protein using an immunoassay test...
July 3, 2018: Antiviral Research
Ren-Rong Tian, Ming-Xu Zhang, Lin-Tao Zhang, Peng Zhang, Jian-Ping Ma, Mingyue Liu, Martin Devenport, Pan Zheng, Xiao-Liang Zhang, Xiao-Dong Lian, Mei Ye, Hong-Yi Zheng, Wei Pang, Gao-Hong Zhang, Li-Guo Zhang, Yang Liu, Yong-Tang Zheng
Chronic immune activation and systemic inflammation are underlying causes of acquired immunodeficiency syndrome (AIDS). Products of virus replication and microbial translocation, co-infection or opportunistic pathogens, and danger-associated molecular patterns have been reported to contribute to chronic immune activation and inflammation in human immunodeficiency virus type-1/simian immunodeficiency virus (HIV-1/SIV) infection or other disease. To develop new strategies and therapies for HIV-1/AIDS, we tested if the CD24 and Fc fusion protein (CD24Fc), which interacts with danger-associated molecular patterns and sialic acid binding Ig-like lectin to attenuate inflammation, can protect Chinese rhesus macaques (ChRMs) with SIV infection...
July 3, 2018: Antiviral Research
Angie Lackenby, Terry G Besselaar, Rod S Daniels, Alicia Fry, Vicki Gregory, Larisa V Gubareva, Weijuan Huang, Aeron C Hurt, Sook-Kwan Leang, Raphael T C Lee, Janice Lo, Lori Lollis, Sebastian Maurer-Stroh, Takato Odagiri, Dmitriy Pereyaslov, Emi Takashita, Dayan Wang, Wenqing Zhang, Adam Meijer
A total of 13672 viruses, collected by World Health Organization recognised National Influenza Centres between May 2016 and May 2017, were assessed for neuraminidase inhibitor susceptibility by four WHO Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance Epidemiology and Control of Influenza. The 50% inhibitory concentration (IC50 ) was determined for oseltamivir and zanamivir for all viruses, and for peramivir and laninamivir in a subset (n = 8457)...
July 3, 2018: Antiviral Research
Febrina Meutiawati, Bodine Bezemer, Jeroen R P M Strating, Gijs J Overheul, Eva Žusinaite, Frank J M van Kuppeveld, Koen W R van Cleef, Ronald P van Rij
Dengue virus (DENV) is associated with an estimated 390 million infections per year, occurring across approximately 100 countries in tropical and sub-tropical regions. To date, there are no antiviral drugs or specific therapies to treat DENV infection. Posaconazole and itraconazole are potent antifungal drugs that inhibit ergosterol biosynthesis in fungal cells, but also target a number of human proteins. Here, we show that itraconazole and posaconazole have antiviral activity against DENV. Posaconazole inhibited replication of multiple serotypes of DENV and the related flavivirus Zika virus, and reduced viral RNA replication, but not translation of the viral genome...
July 2, 2018: Antiviral Research
Sonja I Buschow, Paula J Biesta, Zwier M A Groothuismink, Nicole S Erler, Thomas Vanwolleghem, Erwin Ho, Isabel Najera, Malika Ait-Goughoulte, Rob J de Knegt, Andre Boonstra, Andrea M Woltman
TLR7 agonists are of high interest for the treatment of cancer, auto-immunity and chronic viral infections. They are known to activate plasmacytoid dendritic cells (pDCs) to produce high amounts of Type I Interferon (IFN) and to facilitate T and B cell responses, the latter with the help of maturation markers such as CD40, CD80 and CD86. The TLR7 single nucleotide polymorphism (SNP) rs179008 (GLn11Leu), sex and chronic viral infection have all been reported to influence pDC IFN production. It is unknown, however, whether these factors also influence pDC phenotypic maturation and thereby IFN-independent pDC functions...
June 28, 2018: Antiviral Research
Erik Arabyan, Astghik Hakobyan, Armen Kotsinyan, Zaven Karalyan, Vahram Arakelov, Grigor Arakelov, Karen Nazaryan, Anna Simonyan, Rouben Aroutiounian, Fernando Ferreira, Hovakim Zakaryan
African swine fever virus (ASFV) is the causal agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic consequences in affected countries. Once, neither an anti-viral drug nor an effective vaccines are available, studies on new anti-ASFV molecules are urgently need. Recently, it has been shown that ASFV type II topoisomerase (ASFV-topo II) is inhibited by several fluoroquinolones (bacterial DNA topoisomerase inhibitors), raising the idea that this viral enzyme can be a potential target for drug development against ASFV...
June 22, 2018: Antiviral Research
David W Hawman, Elaine Haddock, Kimberly Meade-White, Brandi Williamson, Patrick W Hanley, Kyle Rosenke, Takashi Komeno, Yousuke Furuta, Brian B Gowen, Heinz Feldmann
Crimean-Congo hemorrhagic fever virus (CCHFV) is a cause of serious hemorrhagic disease in humans. Humans infected with CCHFV develop a non-specific febrile illness and then progress to the hemorrhagic phase where case fatality rates can be as high as 30%. Currently there is lack of vaccines and the recommended antiviral treatment, ribavirin, has inconsistent efficacy in both human and animal studies. In this study we developed a model of CCHFV infection in type I interferon deficient mice using the clinical CCHFV isolate strain Hoti...
June 21, 2018: Antiviral Research
Suvi Heinimäki, Maria Malm, Timo Vesikari, Vesna Blazevic
Rotavirus (RV) inner capsid VP6 protein is a potential non-live vaccine candidate due to high degree of conservation and immunogenicity, and ability to self-assemble into oligomeric structures, including nanotubes. These VP6 structures induce strong humoral and T cell immunity and protect mice against RV challenge. It has been suggested that intracellular neutralization by IgA antibody and VP6-specific CD4+ T cells mediate protection. We investigated generation of diverse CD4+ T cell subsets by intradermal and intranasal delivery of recombinant VP6 (rVP6) nanotubes in BALB/c mice...
June 20, 2018: Antiviral Research
Yuebang Yin, Sunrui Chen, Mohamad S Hakim, Wenshi Wang, Lei Xu, Wen Dang, Changbo Qu, Auke P Verhaar, Junhong Su, Gwenny M Fuhler, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection has emerged as an important cause of complications in organ transplantation recipients and might play a role in the pathogenesis of inflammatory bowel disease (IBD). 6-Thioguanine (6-TG) has been widely used as an immunosuppressive drug for organ recipients and treatment of IBD in the clinic. This study aims to investigate the effects and mode-of-action of 6-TG on rotavirus replication. Human intestinal Caco2 cell line, 3D model of human primary intestinal organoids, laboratory rotavirus strain (SA11) and patient-derived rotavirus isolates were used...
June 16, 2018: Antiviral Research
Kaelin M Bernier, Lynda A Morrison
Herpes simplex virus (HSV)-1 and HSV-2 cause painful blisters and shallow ulcers in exposed skin and mucosae during primary or recurrent infection. In addition, recurrent and potentially blinding HSV-1 infections of the eye afflict nearly half a million persons in the U.S. Current clinical therapies rely on nucleoside analog drugs such as acyclovir (ACV) or ganciclovir to ameliorate primary infections and reduce the frequency and duration of reactivations. However, these treatments do not fully suppress viral shedding and drug-resistant mutants develop in the eye and in vulnerable, immunosuppressed patients...
June 14, 2018: Antiviral Research
Simone La Frazia, Sara Piacentini, Anna Riccio, Jean Francois Rossignol, M Gabriella Santoro
The emergence of new avian influenza virus (AIV) strains able to infect humans represents a serious threat to global human health. In addition to surveillance and vaccine development, antiviral therapy remains crucial for AIV control; however, the increase in drug-resistant AIV strains underscores the need for novel approaches to anti-influenza chemotherapy. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits influenza A/PuertoRico/8/1934(H1N1) virus replication, and this effect was associated with inhibition of viral hemagglutinin (HA) maturation...
June 13, 2018: Antiviral Research
Scott C Weaver
The recent emergence and rapid spread of Zika virus in tropical regions of the Western Hemisphere took arbovirologists and public health officials by surprise, and the earlier transfers of West Nile and chikungunya viruses from the Old to the New World were also unexpected. These pandemics underscore the increasing threat of zoonotic arboviruses, especially those that are capable of entering into human-amplified, urban transmission cycles transmitted by Aedes (Stegomyia) aegypti and sometimes other Aedes (Stegomyia) spp...
June 13, 2018: Antiviral Research
Maria Pujantell, Sandra Franco, Iván Galván-Femenía, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Bonaventura Clotet, Rafael de Cid, Cristina Tural, Miguel A Martínez, Eva Riveira-Muñoz, José A Esté, Ester Ballana
The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I...
June 12, 2018: Antiviral Research
Lisa Bauer, Salvatore Ferla, Sarah A Head, Shridhar Bhat, Kalyan K Pasunooti, Wei Q Shi, Lucian Albulescu, Jun O Liu, Andrea Brancale, Frank J M van Kuppeveld, Jeroen R P M Strating
Itraconazole (ITZ) is a well-known, FDA-approved antifungal drug that is also in clinical trials for its anticancer activity. ITZ exerts its anticancer activity through several disparate targets and pathways. ITZ inhibits angiogenesis by hampering the functioning of the vascular endothelial growth receptor 2 (VEGFR2) and by indirectly inhibiting mTOR signaling. Furthermore, ITZ directly inhibits the growth of several types of tumor cells by antagonizing Hedgehog signaling. Recently, we reported that ITZ also has broad-spectrum antiviral activity against enteroviruses, cardioviruses and hepatitis C virus, independent of established ITZ-activities but instead via a novel target, oxysterol-binding protein (OSBP), a cellular lipid shuttling protein...
May 26, 2018: Antiviral Research
Bernadett Boda, Sacha Benaoudia, Song Huang, Rosy Bonfante, Ludovic Wiszniewski, Eirini D Tseligka, Caroline Tapparel, Samuel Constant
Respiratory viral infections cause mild to severe diseases, such as common cold, bronchiolitis and pneumonia and are associated with substantial burden for society. To test new molecules for shortening, alleviating the diseases or to develop new therapies, relevant human in vitro models are mandatory. MucilAir™, a human standardized air-liquid interface 3D airway epithelial culture holds in vitro specific mechanisms to counter invaders comparable to the in vivo situation, such as mucus production, mucociliary clearance, and secretion of defensive molecules...
August 2018: Antiviral Research
Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J Destache
Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir+tenofovir alafenamide+emtricitabine; EVG+TAF+FTC) drugs (mimicking marketed Genvoya® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs)...
August 2018: Antiviral Research
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