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Antiviral Research

Franck Touret, Cécile Baronti, Olivia Goethals, Marnix Van Loock, Xavier de Lamballerie, Gilles Querat
Dengue 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, currently no approved dengue-specific therapeutic treatments are available. With the aim of providing an efficient tool for dengue virus drug discovery, a collection of nineteen dengue viruses, representing the genotypic diversity within the four serotypes, was developed...
May 11, 2019: Antiviral Research
Naphak Modhiran, Neha S Gandhi, Norbet Wimmer, Stacey Cheung, Katryn Stacey, Paul R Young, Vito Ferro, Daniel Watterson
Dengue 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 attachment, their potential for antiviral intervention in NS1 protein toxicity has not yet been explored...
May 11, 2019: Antiviral Research
Anne-France Georgel, Delphine Cayet, Andrés Pizzorno, Manuel Rosa-Calatrava, Christophe Paget, Valentin Sencio, Jean Dubuisson, François Trottein, Jean-Claude Sirard, Christophe Carnoy
Influenza infections remain a burden on health care systems despite vaccination programs and marketed antiviral drugs. Immunomodulation through activation of innate sensors could represent innovative approaches to fight the flu. 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...
May 9, 2019: Antiviral Research
Edurne Garcia-Vidal, Roger Badia, Maria Pujantell, Marc Castellví, Eudald Felip, Bonaventura Clotet, Eva Riveira-Muñoz, Ester Ballana, José A Esté
Midostaurin 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 flow cytometry in three cell types treated with midostaurin in the presence or absence of SAMHD1. Non-infected cells were treated with midostaurin and harvested for Western blot analysis...
May 8, 2019: Antiviral Research
Tatiana Kotomina, Irina Isakova-Sivak, Victoria Matyushenko, Ki-Hye Kim, Youri Lee, Yu-Jin Jung, Sang-Moo Kang, Larisa Rudenko
Respiratory 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 influenza vaccine (LAIV) might offer an advantage of inducing adequate mucosal CD8 T cell immunity at the infection site of respiratory pathogens...
May 7, 2019: Antiviral Research
Olga Martinez-Arroyo, Aleksandra Gruevska, Victor M Victor, Rosa A Gonzalez-Polo, Sokhna Yakhine-Diop, Jose M Fuentes, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
Efavirenz (EFV), a first generation non-nucleoside analogue reverse transcriptase inhibitor widely employed in combination antiretroviral therapy regimens over the last 20 years, has been associated with a wide range of neuropsychiatric effects and has also been linked with HIV-associated neurocognitive disorder (HAND). EFV has been reported to alter mitochondrial dysfunction and bioenergetics in different cell types, including astrocytes. Here, we analyzed whether this mitochondrial effect is associated with alterations in autophagy and, more specifically, mitophagy...
May 7, 2019: Antiviral Research
Jitra Limthongkul, Nithipong Mapratiep, Suttikarn Apichirapokey, Ampa Suksatu, Panuwat Midoeng, Sukathida Ubol
Dengue viruses (DENVs) have threatened 2/3 of the world population for decades. Thus, combating DENV infection with either antiviral therapy or protective vaccination is an urgent goal. In the present study, we investigated the anti-DENV activity of insect cell-derived anionic septapeptides from C6/36 mosquito cell cultures persistently infected with DENV. These molecules were previously shown to protect C6/36 and Vero cells against DENV infection. We found that treatment with these septapeptides strongly and rapidly downregulated the multiplication of DENV-1 16007, DENV-3 16562, and DENV-4 1036 but not that of DENV-2 16681 in primary human monocytes...
May 7, 2019: Antiviral Research
Zoé Lama, Yves Gaudin, Danielle Blondel, Cécile Lagaudriere-Gesbert
Rabies 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 inhibitors interfere with an early step of viral cycle and can prevent viral replication...
May 6, 2019: Antiviral Research
Satoru Watanabe, Nicole Wei Wen Tan, Kitti Wing Ki Chan, Subhash G Vasudevan
Zika virus (ZIKV) infection during pregnancy has been associated with adverse outcomes and birth defects such as microcephaly in newborn children. Congenital malformations associated with ZIKV are believed to occur via direct infection of the fetus. Unfortunately, there are no licensed therapeutic or preventative tools to block maternal-fetal transmission of ZIKV. 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...
April 30, 2019: Antiviral Research
Shalley N Kudalkar, Irfan Ullah, Nicole Bertoletti, Hanna K Mandl, José A Cisneros, Jagadish Beloor, Albert H Chan, Elias Quijano, W Mark Saltzman, William L Jorgensen, Priti Kumar, Karen S Anderson
Combination antiretroviral therapy (cART) has been proven effective in inhibiting human immunodeficiency virus type 1 (HIV-1) infection and has significantly improved the health outcomes in acquired immune deficiency syndrome (AIDS) patients. The therapeutic benefits of cART have been challenged because of the toxicity and emergence of drug-resistant HIV-1 strains along with lifelong patient compliance resulting in non-adherence. These issues also hinder the clinical benefits of non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are one of the vital components of cART for the treatment of HIV-1 infection...
April 26, 2019: Antiviral Research
He Li, Canrong Zhong, Qian Wang, Weikang Chen, Yan Yuan
Curcumin, 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 phytochemical. However, a concern has been also raised if curcumin has a promiscuous bioassay profile and is a Pan-Assay INterference compound (PAINS)...
April 26, 2019: Antiviral Research
Shirin Nkongolo, Lea Nußbaum, Florian A Lempp, Harald Wodrich, Stephan Urban, Yi Ni
Chronic infection with the human Hepatitis B virus (HBV) is a major global health problem. Hepatitis D virus (HDV) is a satellite of HBV that uses HBV envelope proteins for cell egress and entry. Using infection systems encoding the HBV/HDV receptor human sodium taurocholate co-transporting polypeptide (NTCP), we screened 1181 FDA-approved drugs applying markers for interference for HBV and HDV infection. As one primary hit we identified Acitretin, a retinoid, as an inhibitor of HBV replication and HDV release...
April 21, 2019: Antiviral Research
Subhra Mandal, Pavan Kumar Prathipati, Michael Belshan, Christopher J Destache
Bictegravir (BIC), a newly FDA-approved integrase strand transfer inhibitor (INSTI), as a single tablet regimen has proven efficacious in treating HIV-1 and SIV viruses, with reduced resistance. BIC clinical trials have not investigated its prophylaxis potency. 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 <200 nm in size, with 47...
April 13, 2019: Antiviral Research
Astghik Hakobyan, Erik Arabyan, Armen Kotsinyan, Zaven Karalyan, Harutyun Sahakyan, Vahram Arakelov, Karen Nazaryan, Fernando Ferreira, Hovakim Zakaryan
African 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 significant anti-ASFV activity. However, apigenin is practically insoluble in highly polar solvents and it occurs typically in derivative forms in plants...
April 13, 2019: Antiviral Research
John H Beigel, Hannah H Nam, Peter L Adams, Amy Krafft, William L Ince, Samer S El-Kamary, Amy C Sims
The 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 influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem...
April 8, 2019: Antiviral Research
Sunrui Chen, Shihao Ding, Yuebang Yin, Lei Xu, Pengfei Li, Maikel P Peppelenbosch, Qiuwei Pan, Wenshi Wang
Rotavirus infection remains a great health burden worldwide especially in some developing countries. It causes severe dehydrating diarrhea in infants, young children, as well as immunocompromised and organ transplanted patients. Viral replication heavily relies on the host to supply nucleosides. Thus, host enzymes involved in nucleotide biosynthesis represent potential targets for antiviral development. Dihydroorotate dehydrogenase (DHODH) is the rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines...
April 8, 2019: Antiviral Research
Colleen B Jonsson, Xufeng Cao, Jasper Lee, Jon D Gabbard, Yong-Kyu Chu, Elizabeth A Fitzpatrick, Justin Julander, Dong-Hoon Chung, Jennifer Stabenow, Jennifer E Golden
Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV)...
April 7, 2019: Antiviral Research
Jia Le Lee, Marcus Wing Choy Loe, Regina Ching Hua Lee, Justin Jang Hann Chu
Zika virus (ZIKV) is a mosquito-borne virus that has garnered a lot of attention in recent years, due to the explosive epidemic from 2014 to 2016. Since its introduction in the Americas in late 2014, ZIKV has spread at an unprecedented rate and scale throughout the world and infected millions of people. Its infection has also been associated with severe neurological disorders like Guillain-Barré syndrome and microcephaly in fetuses. Despite these, there is currently no approved antiviral against ZIKV. In this study, an immunofluorescence-based high throughput screen was conducted on a library of 483 flavonoid derivatives to identify potential anti-ZIKV compounds...
April 5, 2019: Antiviral Research
Xiaoyu Zhang, Feihu Yan, Ke Tang, Qing Chen, Jiamei Guo, Wenjun Zhu, Shihua He, Logan Banadyga, Xiangguo Qiu, Ying Guo
Lassa virus (LASV) causes Lassa hemorrhagic fever in humans and poses a significant threat to public health in West Africa. Current therapeutic treatments for Lassa fever are limited, making the development of novel countermeasures an urgent priority. 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...
April 3, 2019: Antiviral Research
Vimbaishe P Chibanga, Larissa Dirr, Patrice Guillon, Ibrahim M El-Deeb, Benjamin Bailly, Robin J Thomson, Mark von Itzstein
Human parainfluenza viruses cause acute respiratory tract infections and disease predominantly in young children and immunocompromised individuals. Currently, there are no vaccines to prevent hPIV infections, nor licensed anti-hPIV drugs. There is therefore a need for specific antiviral therapies to decrease the morbidity and mortality associated with hPIV diseases. Haemagglutinin-neuraminidase (HN) is one of two hPIV surface proteins with critical roles in host receptor recognition, binding and cleavage; it has been explored as a key drug development target for the past five decades with variable success...
April 2, 2019: Antiviral Research
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