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https://www.readbyqxmd.com/read/28077633/surveillance-of-bat-coronaviruses-in-kenya-identifies-relatives-of-human-coronaviruses-nl63-and-229e-and-their-recombination-history
#1
Ying Tao, Mang Shi, Christina Chommanard, Krista Queen, Jing Zhang, Wanda Markotter, Ivan V Kuzmin, Edward C Holmes, Suxiang Tong
: Bats harbor a large diversity of coronaviruses (CoVs), several of which are related to zoonotic pathogens that cause severe disease in humans. Our screening of bat samples collected in Kenya during 2007-2010 not only detected RNA from several novel CoVs but, more significantly, identified sequences that were closely related to human CoVs NL63 and 229E, suggesting that these two human viruses originate from bats. We also demonstrated that human CoV NL63 is a recombinant between NL63-like viruses circulating in Triaenops bats and 229E-like viruses circulating in Hipposideros bats, with the break-point located near 5' and 3' end of the spike (S) protein gene...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28038326/design-synthesis-and-evaluation-of-a-novel-series-of-macrocyclic-inhibitors-of-norovirus-3cl-protease
#2
Vishnu C Damalanka, Yunjeong Kim, Anushka C Galasiti Kankanamalage, Gerald H Lushington, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Kyeong-Ok Chang, William C Groutas
Norovirus infections have a major impact on public health worldwide, yet there is a current dearth of norovirus-specific therapeutics and prophylactics. This report describes the discovery of a novel class of macrocyclic inhibitors of norovirus 3C-like protease, a cysteine protease that is essential for virus replication. SAR, structural, and biochemical studies were carried out to ascertain the effect of structure on pharmacological activity and permeability. Insights gained from these studies have laid a solid foundation for capitalizing on the therapeutic potential of the series of inhibitors described herein...
December 21, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28004946/fluorescent-inhibitors-as-tools-to-characterize-enzymes-case-study-of-the-lipid-kinase-phosphatidylinositol-4-kinase-iii%C3%AE-pi4kb
#3
Jana Humpolickova, Ivana Mejdrová, Marika Matousova, Radim Nencka, Evzen Boura
The lipid kinase phosphatidylinositol 4-kinase IIIβ (PI4KB) is an essential host factor for many positive-sense single-stranded RNA (+RNA) viruses including human pathogens hepatitis C virus (HCV), Severe acute respiratory syndrome (SARS), coxsackie viruses, and rhinoviruses. Inhibitors of PI4KB are considered to be potential broad-spectrum virostatics, and it is therefore critical to develop a biochemical understanding of the kinase. Here, we present highly potent and selective fluorescent inhibitors that we show to be useful chemical biology tools especially in determination of dissociation constants...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28003490/lineage-a-betacoronavirus-ns2-proteins-and-homologous-torovirus-berne-pp1a-carboxyterminal-domain-are-phosphodiesterases-that-antagonize-activation-of-rnase-l
#4
Stephen A Goldstein, Joshua M Thornbrough, Rong Zhang, Babal K Jha, Yize Li, Ruth Elliott, Katherine Quiroz-Figueroa, Annie I Chen, Robert H Silverman, Susan R Weiss
: Viruses in the family Coronaviridae, with the Nidovirus order, are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory disease in humans. These viruses encode conserved replicase and structural proteins, and more diverse accessory proteins in the 3' end of their genomes that often act as host cell antagonists. We have previously shown that 2', 5' phosphodiesterases (PDE) encoded by the prototypical Betacoronavirus, mouse hepatitis virus (MHV), Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate - ribonuclease L (OAS-RNase L) pathway...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27999325/pharmacokinetics-of-the-antiviral-lectin-griffithsin-administered-by-different-routes-indicates-multiple-potential-uses
#5
Christopher Barton, J Calvin Kouokam, Harrell Hurst, Kenneth E Palmer
Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points...
December 17, 2016: Viruses
https://www.readbyqxmd.com/read/27999271/use-of-aptamers-as-diagnostics-tools-and-antiviral-agents-for-human-viruses
#6
REVIEW
Víctor M González, M Elena Martín, Gerónimo Fernández, Ana García-Sacristán
Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins...
December 16, 2016: Pharmaceuticals
https://www.readbyqxmd.com/read/27989113/optimization-and-synthesis-of-pyridazinone-derivatives-as-novel-inhibitors-of-hepatitis-b-virus-by-inducing-genome-free-capsid-formation
#7
Dong Lu, Feifei Liu, Weiqiang Xing, Xiankun Tong, Lang Wang, Yajuan Wang, Limin Zeng, Chunlan Feng, Li Yang, Jianping Zuo, Youhong Hu
The capsid of hepatitis B virus (HBV) plays a vital role in virus DNA replication. Targeting nucleocapsid function has been demonstrated as an effective approach for anti-HBV drug development. A high-throughput screening and mechanism study revealed the hit compound 4a as an HBV assembly effector (AEf), which could inhibit HBV replication by inducing the formation of HBV DNA-free capsids. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0...
December 29, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27974570/channel-inactivating-mutations-and-their-revertant-mutants-in-the-envelope-protein-of-the-infectious-bronchitis-virus
#8
Janet To, Wahyu Surya, To Sing Fung, Yan Li, Carmina Verdià-Bàguena, Maria Queralt-Martin, Vicente M Aguilella, Ding Xiang Liu, Jaume Torres
: It has been shown previously in the severe acute respiratory syndrome coronavirus (SARS-CoV) that two point mutations, N15A and V25F, in the transmembrane domain (TMD) of the envelope (E) protein abolished channel activity and led to in vivo attenuation. Pathogenicity was recovered in mutants that also regained E protein channel activity. In particular, V25F was rapidly compensated by changes at multiple V25F-facing TMD residues located on a neighboring monomer, consistent with a recovery of oligomerization...
December 14, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27966107/the-middle-east-respiratory-syndrome-coronavirus-a-continuing-risk-to-global-health-security
#9
Esam I Azhar, Simone Lanini, Giuseppe Ippolito, Alimuddin Zumla
Two new zoonotic coronaviruses causing disease in humans (Zumla et al. 2015a; Hui and Zumla 2015; Peiris et al. 2003; Yu et al. 2014) have been the focus of international attention for the past 14 years due to their epidemic potential; (1) The Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) (Peiris et al. 2003) first discovered in China in 2001 caused a major global epidemic of the Severe Acute Respiratory Syndrome (SARS). (2) The Middle East respiratory syndrome coronavirus (MERS-CoV) is a new corona virus isolated for the first time in a patients who died of severe lower respiratory tract infection in Jeddah (Saudi Arabia) in June 2012 (Zaki et al...
December 14, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27965448/the-conserved-coronavirus-macrodomain-promotes-virulence-and-suppresses-the-innate-immune-response-during-severe-acute-respiratory-syndrome-coronavirus-infection
#10
Anthony R Fehr, Rudragouda Channappanavar, Gytis Jankevicius, Craig Fett, Jincun Zhao, Jeremiah Athmer, David K Meyerholz, Ivan Ahel, Stanley Perlman
: ADP-ribosylation is a common posttranslational modification that may have antiviral properties and impact innate immunity. To regulate this activity, macrodomain proteins enzymatically remove covalently attached ADP-ribose from protein targets. All members of the Coronavirinae, a subfamily of positive-sense RNA viruses, contain a highly conserved macrodomain within nonstructural protein 3 (nsp3). However, its function or targets during infection remain unknown. We identified several macrodomain mutations that greatly reduced nsp3's de-ADP-ribosylation activity in vitro Next, we created recombinant severe acute respiratory syndrome coronavirus (SARS-CoV) strains with these mutations...
December 13, 2016: MBio
https://www.readbyqxmd.com/read/27956136/prophylactic-and-therapeutic-intranasal-administration-with-an-immunomodulator-hiltonol-%C3%A2-poly-ic-lc-in-a-lethal-sars-cov-infected-balb-c-mouse-model
#11
Yohichi Kumaki, Andres M Salazar, Miles K Wandersee, Dale L Barnard
Hiltonol(®), (Poly IC:LC), a potent immunomodulator, is a synthetic, double-stranded polyriboinosinic-polyribocytidylic acid (poly IC) stabilized with Poly-L-lysine and carboxymethyl cellulose (LC). Hiltonol(®) was tested for efficacy in a lethal SARS-CoV-infected BALB/c mouse model. Hiltonol(®) at 5, 1, 0.5 or 0.25 mg/kg/day by intranasal (i.n.) route resulted in significant survival benefit when administered at selected times 24 h prior to challenge with a lethal dose of mouse-adapted severe acute respiratory syndrome coronavirus (SARS-CoV)...
December 9, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27943331/genomic-investigation-of-piglet-resilience-following-porcine-epidemic-diarrhea-outbreaks
#12
F Bertolini, J C S Harding, B Mote, A Ladinig, G S Plastow, M F Rothschild
Porcine epidemic diarrhea virus (PEDV) belongs to the Coronaviridae family and causes malabsorptive watery diarrhea, vomiting, dehydration and imbalanced blood electrolytes in pigs. Since the 1970s, PED outbreaks have become a source of problems in pig producing countries all over the world, causing large economic losses for pig producers. Although the infection in adults is not fatal, in naïve suckling piglets mortality is close to 100%. In this study, we investigated genome-wide differences between dead and recovered suckling piglets from commercial farms after PED outbreaks...
December 12, 2016: Animal Genetics
https://www.readbyqxmd.com/read/27934903/unlocking-bat-immunology-establishment-of-pteropus-alecto-bone-marrow-derived-dendritic-cells-and-macrophages
#13
Peng Zhou, Yok Teng Chionh, Sergio Erdal Irac, Matae Ahn, Justin Han Jia Ng, Even Fossum, Bjarne Bogen, Florent Ginhoux, Aaron T Irving, Charles-Antoine Dutertre, Lin-Fa Wang
Bats carry and shed many emerging infectious disease agents including Ebola virus and SARS-like Coronaviruses, yet they rarely display clinical symptoms of infection. Bat epithelial or fibroblast cell lines were previously established to study the bat immune response against viral infection. However, the lack of professional immune cells such as dendritic cells (DC) and macrophages has greatly limited the significance of current investigations. Using Pteropus alecto (P. alecto) GM-CSF plus IL4, FLT3L and CSF-1, we successfully generated bat bone marrow-derived DC and macrophages...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932284/genetic-diversity-of-coronaviruses-in-bats-in-lao-pdr-and-cambodia
#14
Audrey Lacroix, Veasna Duong, Vibol Hul, Sorn San, Hull Davun, Keo Omaliss, Sokha Chea, Alexandre Hassanin, Watthana Theppangna, Soubanh Silithammavong, Kongsy Khammavong, Sinpakone Singhalath, Zoe Greatorex, Amanda E Fine, Tracey Goldstein, Sarah Olson, Damien O Joly, Lucy Keatts, Philippe Dussart, Aneta Afelt, Roger Frutos, Philippe Buchy
South-East Asia is a hot spot for emerging zoonotic diseases, and bats have been recognized as hosts for a large number of zoonotic viruses such as Severe Acute Respiratory Syndrome (SARS), responsible for acute respiratory syndrome outbreaks. Thus, it is important to expand our knowledge of the presence of viruses in bats which could represent a risk to humans. Coronaviruses (CoVs) have been reported in bat species from Thailand, China, Indonesia, Taiwan and the Philippines. However no such work was conducted in Cambodia or Lao PDR...
December 6, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27928918/characterization-and-phylogenetic-analysis-of-new-bat-astroviruses-detected-in-gabon-central-africa
#15
V Rougeron, E Suquet, G D Maganga, D Jiolle, I M Mombo, M Bourgarel, P Motsch, C Arnathau, P Durand, F Drexler, C Drosten, F Renaud, F Prugnolle, E M Leroy
Astroviruses are emerging RNA viruses that cause enteropathogenic infections in humans and in other mammals. The identification of astroviruses in a wide range of animals highlights the zoonotic importance of these viruses. Bats can harbor many different viruses, among which some are highly pathogenic for humans (for instance, Nipah, Ebola and SARS coronavirus), and also several astroviruses. As some RNA viruses can be directly transmitted from bats to humans, it is crucial to collect data about their frequency, genetic diversity and phylogenetic characterization...
2016: Acta Virologica
https://www.readbyqxmd.com/read/27892522/sars-cov-fusion-peptides-induce-membrane-surface-ordering-and-curvature
#16
Luis G M Basso, Eduardo F Vicente, Edson Crusca, Eduardo M Cilli, Antonio J Costa-Filho
Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880744/notice-to-readers-final-2015-reports-of-nationally-notifiable-infectious-diseases-and-conditions
#17
(no author information available yet)
The table listed in this report on pages 1307-1321 presents finalized data, as of June 30, 2016, from the National Notifiable Diseases Surveillance System (NNDSS) for 2015. These data will be published in more detail in the Summary of Notifiable Infectious Diseases and Conditions - United States, 2015 (1). Because no cases were reported in the United States during 2015, the following diseases do not appear in this early release table: anthrax; dengue hemorrhagic fever; diphtheria; eastern equine encephalitis virus disease, nonneuroinvasive; poliomyelitis, paralytic; poliovirus infection, nonparalytic; severe acute respiratory syndrome-associated coronavirus disease (SARS-CoV); smallpox; western equine encephalitis virus disease, neuroinvasive and nonneuroinvasive; yellow fever; and viral hemorrhagic fevers...
November 25, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27864902/quantitative-structure-activity-relationship-and-molecular-docking-revealed-a-potency-of-anti-hepatitis-c-virus-drugs-against-human-corona-viruses
#18
Abdo A Elfiky, Samah M Mahdy, Wael M Elshemey
A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (e.g. SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins...
November 19, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27847245/celastrol-inhibits-dengue-virus-replication-via-up-regulating-type-i-interferon-and-downstream-interferon-stimulated-responses
#19
Jung-Sheng Yu, Chin-Kai Tseng, Chun-Kuang Lin, Yao-Chin Hsu, Yu-Hsuan Wu, Ching-Liang Hsieh, Jin-Ching Lee
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27823624/antitumor-lignanamides-from-the-aerial-parts-of-corydalis-saxicola
#20
Bin Zhang, Rizhen Huang, Jing Hua, Hong Liang, Yingming Pan, Lumei Dai, Dong Liang, Hengshan Wang
BACKGROUND: Cancer is one of the leading cause of unnatural death globally. There is still a great need for effective anticancer agents from plant sources. Corydalis saxicola Bunting is a medicinal plant that is traditionally used to treat various diseases in southwest China. Previous phytochemical investigations of C. saxicola have focused on isoquinoline alkaloids that have been isolated, which have activity against anti-hepatitis B virus and inhibit DNA topoisomerase I. However, the exploration of other classes of constituents and their bioactivities needs further study...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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