Ribavirin Inhibits West Nile Virus Replication and Cytopathic Effect in Neural Cells
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Establishment of a Cell Culture Model of Persistent Flaviviral Infection: Usutu Virus Shows Sustained Replication During Passage
viruses Article Establishment of a Cell Culture Model of Persistent Flaviviral Infection: Usutu Virus Shows Sustained Replication during Passages and Resistance to Extinction by Antiviral Nucleosides Raquel Navarro Sempere 1,2 and Armando Arias 1,* 1 Life Science & Bioengineering Building, Technical University of Denmark, 2800 Kongens Lyngby, Denmark; [email protected] 2 Abiopep Sociedad Limitada, Parque Científico de Murcia, 30100 Murcia, Spain * Correspondence: [email protected] Received: 22 March 2019; Accepted: 15 June 2019; Published: 17 June 2019 Abstract: Chronic viral disease constitutes a major global health problem, with several hundred million people affected and an associated elevated number of deaths. An increasing number of disorders caused by human flaviviruses are related to their capacity to establish a persistent infection. Here we show that Usutu virus (USUV), an emerging zoonotic flavivirus linked to sporadic neurologic disease in humans, can establish a persistent infection in cell culture. Two independent lineages of Vero cells surviving USUV lytic infection were cultured over 82 days (41 cell transfers) without any apparent cytopathology crisis associated. We found elevated titers in the supernatant of these cells, with modest fluctuations during passages but no overall tendency towards increased or decreased infectivity. In addition to full-length genomes, viral RNA isolated from these cells at passage 40 revealed the presence of defective genomes, containing different deletions at the 5’ end. These truncated transcripts were all predicted to encode shorter polyprotein products lacking membrane and envelope structural proteins, and most of non-structural protein 1. Treatment with different broad-range antiviral nucleosides revealed that USUV is sensitive to these compounds in the context of a persistent infection, in agreement with previous observations during lytic infections. -
Multiple Origins of Viral Capsid Proteins from Cellular Ancestors
Multiple origins of viral capsid proteins from PNAS PLUS cellular ancestors Mart Krupovica,1 and Eugene V. Kooninb,1 aInstitut Pasteur, Department of Microbiology, Unité Biologie Moléculaire du Gène chez les Extrêmophiles, 75015 Paris, France; and bNational Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894 Contributed by Eugene V. Koonin, February 3, 2017 (sent for review December 21, 2016; reviewed by C. Martin Lawrence and Kenneth Stedman) Viruses are the most abundant biological entities on earth and show genome replication. Understanding the origin of any virus group is remarkable diversity of genome sequences, replication and expres- possible only if the provenances of both components are elucidated sion strategies, and virion structures. Evolutionary genomics of (11). Given that viral replication proteins often have no closely viruses revealed many unexpected connections but the general related homologs in known cellular organisms (6, 12), it has been scenario(s) for the evolution of the virosphere remains a matter of suggested that many of these proteins evolved in the precellular intense debate among proponents of the cellular regression, escaped world (4, 6) or in primordial, now extinct, cellular lineages (5, 10, genes, and primordial virus world hypotheses. A comprehensive 13). The ability to transfer the genetic information encased within sequence and structure analysis of major virion proteins indicates capsids—the protective proteinaceous shells that comprise the that they evolved on about 20 independent occasions, and in some of cores of virus particles (virions)—is unique to bona fide viruses and these cases likely ancestors are identifiable among the proteins of distinguishes them from other types of selfish genetic elements cellular organisms. -
A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses
A preliminary study of viral metagenomics of French bat species in contact with humans: identification of new mammalian viruses. Laurent Dacheux, Minerva Cervantes-Gonzalez, Ghislaine Guigon, Jean-Michel Thiberge, Mathias Vandenbogaert, Corinne Maufrais, Valérie Caro, Hervé Bourhy To cite this version: Laurent Dacheux, Minerva Cervantes-Gonzalez, Ghislaine Guigon, Jean-Michel Thiberge, Mathias Vandenbogaert, et al.. A preliminary study of viral metagenomics of French bat species in contact with humans: identification of new mammalian viruses.. PLoS ONE, Public Library of Science, 2014, 9 (1), pp.e87194. 10.1371/journal.pone.0087194.s006. pasteur-01430485 HAL Id: pasteur-01430485 https://hal-pasteur.archives-ouvertes.fr/pasteur-01430485 Submitted on 9 Jan 2017 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License A Preliminary Study of Viral Metagenomics of French Bat Species in Contact with Humans: Identification of New Mammalian Viruses Laurent Dacheux1*, Minerva Cervantes-Gonzalez1, -
Isolation and Classification of Feline Picornavirus and Herpes- Virus in Denmark*
Acta vet. scand. 1972, 13, 462-471. From the Small Animal Clinic, Royal Veterinary and Agricultural University, Copenhagen, Denmark. ISOLATION AND CLASSIFICATION OF FELINE PICORNAVIRUS AND HERPES VIRUS IN DENMARK* By A. Flagstad FLAGSTAD, A.: Isolation and classification of feline picornavirus and herpesvirus in Denmark. Acta vet. scand. 1972, 13, 462-471. Seventeen viral isolates cytopathic for kitten kidney cells were isolated from 23 cats with symptoms of the respiratory disease feline viral rhinotracheitis or feline influenza. Five of these are classified ten tatively as calicivirus, a member of the picornavirus group, and 12 have the properties of the herpesvirus. Classification is based on the cytopathic effect in cell cultures and physico-chemical characteristics. The five isolates which are classified tentatively as calicivirus produced a quick cytopathic effect without formation of intranuclear inclusion bodies. The isolates were resistant to chloroform, were not inhibited by IDU, were labile at pH 4 and were not stabilized against thermal inactivation by molar MgCI2. The 12 isolates which seem to belong to the herpesvirus produced intranuclear inclusion bodies in cell cultures. They were sensitive to chloroform, and multiplication was inhibited by IDU. Antisera were produced by inoculating rabbits with calicivirus and cats with herpesvirus. The five isolates classified tentatively as calicivirus belong in one serotype, and the 12 isolates which seem to belong to the herpesvirus also belong in one serotype. f eli n e pic 0 rna vir u s; f eli n e c a I i c i vir u s; f eli n e her pes vir u s; f eli n e vir a I r h i not r a c he i tis; f eli n e i n flu e n z a; i sol a t ion; c I ass i f i cat ion; Den mar k. -
And Giant Guitarfish (Rhynchobatus Djiddensis)
VIRAL DISCOVERY IN BLUEGILL SUNFISH (LEPOMIS MACROCHIRUS) AND GIANT GUITARFISH (RHYNCHOBATUS DJIDDENSIS) BY HISTOPATHOLOGY EVALUATION, METAGENOMIC ANALYSIS AND NEXT GENERATION SEQUENCING by JENNIFER ANNE DILL (Under the Direction of Alvin Camus) ABSTRACT The rapid growth of aquaculture production and international trade in live fish has led to the emergence of many new diseases. The introduction of novel disease agents can result in significant economic losses, as well as threats to vulnerable wild fish populations. Losses are often exacerbated by a lack of agent identification, delay in the development of diagnostic tools and poor knowledge of host range and susceptibility. Examples in bluegill sunfish (Lepomis macrochirus) and the giant guitarfish (Rhynchobatus djiddensis) will be discussed here. Bluegill are popular freshwater game fish, native to eastern North America, living in shallow lakes, ponds, and slow moving waterways. Bluegill experiencing epizootics of proliferative lip and skin lesions, characterized by epidermal hyperplasia, papillomas, and rarely squamous cell carcinoma, were investigated in two isolated poopulations. Next generation genomic sequencing revealed partial DNA sequences of an endogenous retrovirus and the entire circular genome of a novel hepadnavirus. Giant Guitarfish, a rajiform elasmobranch listed as ‘vulnerable’ on the IUCN Red List, are found in the tropical Western Indian Ocean. Proliferative skin lesions were observed on the ventrum and caudal fin of a juvenile male quarantined at a public aquarium following international shipment. Histologically, lesions consisted of papillomatous epidermal hyperplasia with myriad large, amphophilic, intranuclear inclusions. Deep sequencing and metagenomic analysis produced the complete genomes of two novel DNA viruses, a typical polyomavirus and a second unclassified virus with a 20 kb genome tentatively named Colossomavirus. -
Potential Drug Candidates Underway Several Registered Clinical Trials for Battling COVID-19
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 20 April 2020 doi:10.20944/preprints202004.0367.v1 Potential Drug Candidates Underway Several Registered Clinical Trials for Battling COVID-19 Fahmida Begum Minaa, Md. Siddikur Rahman¥a, Sabuj Das¥a, Sumon Karmakarb, Mutasim Billahc* aDepartment of Genetic Engineering and Biotechnology, University of Rajshahi, Rajshahi-6205, Bangladesh bMolecular Biology and Protein Science Laboratory, University of Rajshahi, Rajshahi-6205, Bangladesh cProfessor Joarder DNA & Chromosome Research Laboratory, University of Rajshahi, Rajshahi-6205, Bangladesh *Corresponding Author: Mutasim Billah, Professor Joarder DNA & Chromosome Research Laboratory, University of Rajshahi, Rajshahi, Bangladesh Corresponding Author Mail: [email protected] ¥Co-second author Abstract The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019- nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices. Keywords: COVID-19; Drugs; 2019-nCoV; Clinical trials; SARS-CoV-2 Introduction A new type of viral pneumonia cases occurred in Wuhan, Hubei Province in China, on December 31, 2019; named "COVID-19" on January 12, 2020 by the World Health Organization (WHO) [1]. -
Stems for Nonproprietary Drug Names
USAN STEM LIST STEM DEFINITION EXAMPLES -abine (see -arabine, -citabine) -ac anti-inflammatory agents (acetic acid derivatives) bromfenac dexpemedolac -acetam (see -racetam) -adol or analgesics (mixed opiate receptor agonists/ tazadolene -adol- antagonists) spiradolene levonantradol -adox antibacterials (quinoline dioxide derivatives) carbadox -afenone antiarrhythmics (propafenone derivatives) alprafenone diprafenonex -afil PDE5 inhibitors tadalafil -aj- antiarrhythmics (ajmaline derivatives) lorajmine -aldrate antacid aluminum salts magaldrate -algron alpha1 - and alpha2 - adrenoreceptor agonists dabuzalgron -alol combined alpha and beta blockers labetalol medroxalol -amidis antimyloidotics tafamidis -amivir (see -vir) -ampa ionotropic non-NMDA glutamate receptors (AMPA and/or KA receptors) subgroup: -ampanel antagonists becampanel -ampator modulators forampator -anib angiogenesis inhibitors pegaptanib cediranib 1 subgroup: -siranib siRNA bevasiranib -andr- androgens nandrolone -anserin serotonin 5-HT2 receptor antagonists altanserin tropanserin adatanserin -antel anthelmintics (undefined group) carbantel subgroup: -quantel 2-deoxoparaherquamide A derivatives derquantel -antrone antineoplastics; anthraquinone derivatives pixantrone -apsel P-selectin antagonists torapsel -arabine antineoplastics (arabinofuranosyl derivatives) fazarabine fludarabine aril-, -aril, -aril- antiviral (arildone derivatives) pleconaril arildone fosarilate -arit antirheumatics (lobenzarit type) lobenzarit clobuzarit -arol anticoagulants (dicumarol type) dicumarol -
Antiviral Agents Against African Swine Fever Virus T ⁎ Erik Arabyan, Armen Kotsynyan, Astghik Hakobyan, Hovakim Zakaryan
Virus Research 270 (2019) 197669 Contents lists available at ScienceDirect Virus Research journal homepage: www.elsevier.com/locate/virusres Review Antiviral agents against African swine fever virus T ⁎ Erik Arabyan, Armen Kotsynyan, Astghik Hakobyan, Hovakim Zakaryan Group of Antiviral Defense Mechanisms, Institute of Molecular Biology of NAS, Yerevan, Armenia ARTICLE INFO ABSTRACT Keywords: African swine fever virus (ASFV) is a significant transboundary virus that continues to spread outside Africa in African swine fever virus Europe and most recently to China, Vietnam and Cambodia. Pigs infected with highly virulent ASFV develop a Antiviral hemorrhagic fever like illness with high lethality reaching up to 100%. There are no vaccines or antiviral drugs Flavonoid available for the prevention or treatment of ASFV infections. We here review molecules that have been reported Nucleoside to inhibit ASFV replication, either as direct-acting antivirals or host-targeting drugs as well as those that act via a Pig yet unknown mechanism. Prospects for future antiviral research against ASFV are also discussed. 1. Introduction as HIV and hepatitis B virus infections. Nevertheless, there is still no antiviral drug for more than 200 viruses affecting human populations African swine fever (ASF) is one of the most important swine dis- worldwide (De Clercq and Li, 2016). Moreover, control of some animal eases due to its significant socioeconomic consequences for affected viruses like ASFV by means of an antiviral therapy appears to be an countries. It was first observed in Kenya in the early 20th century fol- attractive approach due to the lack of other control measures. There- lowing the introduction into the country of European domestic swine. -
Phylogenetic Analysis and Transmission Cycle of Tick-Borne Encephalitis Virus Isolated in Hokkaido
Title Phylogenetic analysis and transmission cycle of tick-borne encephalitis virus isolated in Hokkaido Author(s) HAYASAKA, Daisuke Citation Japanese Journal of Veterinary Research, 46(2-3), 159-160 Issue Date 1998-11-30 Doc URL http://hdl.handle.net/2115/2711 Type bulletin (article) File Information KJ00003408044.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP lPn. l. Vet. Res. 46(2-3), (1998) Information 159 Establishment of monoclonal antibodies against Borna disease virus p40 protein and the application to a serological diagnostic method Kouji Tsujimura Laboratory of Public Health, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicene, Hokkaido University, Sapporo 060-0818, Japan Borna disease causes polioencephalomyelitis protein of BDV were obtained using recombinant of horses and sheep. The disease has been p40 protein as the immunogen. These MAbs known to be endemic in Central Europe. Re were confirmed to be reactive to native p40 centely, seroepidemiological survey of the causa protein by Immunofluorescent antibody assay tive agent (Borna disease virus, BDV) suggests (IF A) using MDCK cells persistently infected that the virus distributes in wide areas among with BDV. differernt spicies of animals and is also suspected 2. The MAbs were separated into three groups to be associated with human psychiatric dis from reactivity to p40 in Western blot analysis. orders. It is important to search the reservoir B9 and E7 of group 1 can detect the virus antigen animal, however there is no standard seological in persistently infected rat brain. These two diagnostic method for BDV infection and the MAbs recognized different epitopes. -
Metagenomic Identification of Diverse Animal Hepaciviruses and Pegiviruses
bioRxiv preprint doi: https://doi.org/10.1101/2020.05.16.100149; this version posted May 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Metagenomic identification of diverse animal hepaciviruses and 2 pegiviruses 3 4 5 Ashleigh F. Porter1, John H.-O. Pettersson1,2, Wei-Shan Chang1, Erin Harvey1, Karrie Rose3, 6 Mang Shi5, John-Sebastian Eden1,4, Jan Buchmann1, Craig Moritz6, Edward C. Holmes1 7 8 9 1. Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and 10 Environmental Sciences and School of Medical Sciences, The University of Sydney, 11 Sydney, Australia. 12 2. Zoonosis Science Center, Department of Medical Biochemistry and Microbiology, 13 Uppsala University, Uppsala, Sweden. 14 3. Australian Registry of Wildlife Health, Taronga Conservation Society Australia, 15 Mosman, Australia. 16 4. Centre for Virus Research, Westmead Institute for Medical Research, Westmead, 17 Australia. 18 5. School of Medicine, Sun Yat-sen University, Guangzhou, China. 19 6. Research School of Biology, and Centre for Biodiversity Analysis, Australian National 20 University, Acton, ACT, Australia. 21 22 23 Address correspondence to: 24 Edward C. Holmes, 25 Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and 26 Environmental Sciences and School of Medical Sciences, The University of Sydney, 27 Sydney, Australia 28 [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.05.16.100149; this version posted May 17, 2020. -
WO 2015/061752 Al 30 April 2015 (30.04.2015) P O P CT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/061752 Al 30 April 2015 (30.04.2015) P O P CT (51) International Patent Classification: Idit; 816 Fremont Street, Apt. D, Menlo Park, CA 94025 A61K 39/395 (2006.01) A61P 35/00 (2006.01) (US). A61K 31/519 (2006.01) (74) Agent: HOSTETLER, Michael, J.; Wilson Sonsini (21) International Application Number: Goodrich & Rosati, 650 Page Mill Road, Palo Alto, CA PCT/US20 14/062278 94304 (US). (22) International Filing Date: (81) Designated States (unless otherwise indicated, for every 24 October 2014 (24.10.2014) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (25) Filing Language: English BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (26) Publication Language: English DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (30) Priority Data: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, 61/895,988 25 October 2013 (25. 10.2013) US MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 61/899,764 4 November 2013 (04. 11.2013) US PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 61/91 1,953 4 December 2013 (04. 12.2013) us SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 61/937,392 7 February 2014 (07.02.2014) us TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. -
Borna Disease Virus Infection in Animals and Humans
Synopses Borna Disease Virus Infection in Animals and Humans Jürgen A. Richt,* Isolde Pfeuffer,* Matthias Christ,* Knut Frese,† Karl Bechter,‡ and Sibylle Herzog* *Institut für Virologie, Giessen, Germany; †Institut für Veterinär-Pathologie, Giessen, Germany; and ‡Universität Ulm, Günzburg, Germany The geographic distribution and host range of Borna disease (BD), a fatal neuro- logic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell–mediated immune reaction. Because antibodies reactive with BDV have been found in the sera of patients with neuro- psychiatric disorders, this review examines the possible link between BDV and such disorders. Seroepidemiologic and cerebrospinal fluid investigations of psychiatric patients suggest a causal role of BDV infection in human psychiatric disorders. In diagnostically unselected psychiatric patients, the distribution of psychiatric disorders was found to be similar in BDV seropositive and seronegative patients. In addition, BDV-seropositive neurologic patients became ill with lymphocytic meningoencephali- tis. In contrast to others, we found no evidence is reported for BDV RNA, BDV antigens, or infectious BDV in peripheral blood cells of psychiatric patients. Borna disease (BD), first described more predilection for the gray matter of the cerebral than 200 years ago in southern Germany as a hemispheres and the brain stem (8,19).