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https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#1
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28187135/pathogen-cross-transmission-via-building-sanitary-plumbing-systems-in-a-full-scale-pilot-test-rig
#2
Michael Gormley, Thomas J Aspray, David A Kelly, Cristina Rodriguez-Gil
The WHO Consensus Document on the epidemiology of the SARS epidemic in 2003, included a report on a concentrated outbreak in one Hong Kong housing block which was considered a 'super-spreading event'. The WHO report conjectured that the sanitary plumbing system was one transmission route for the virus. Empty U-traps allowed the aerosolised virus to enter households from the sewerage system. No biological evidence was presented. This research reports evidence that pathogens can be aerosolised and transported on airstreams within sanitary plumbing systems and enter buildings via empty U-traps...
2017: PloS One
https://www.readbyqxmd.com/read/28159412/new-tools-in-nucleoside-toolbox-of-tick-borne-encephalitis-virus-reproduction-inhibitors
#3
Alexey A Orlov, Mikhail S Drenichev, Vladimir E Oslovsky, Nikolay N Kurochkin, Pavel N Solyev, Liubov I Kozlovskaya, Vladimir A Palyulin, Galina G Karganova, Sergey N Mikhailov, Dmitry I Osolodkin
Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5'...
January 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28158275/early-endonuclease-mediated-evasion-of-rna-sensing-ensures-efficient-coronavirus-replication
#4
Eveline Kindler, Cristina Gil-Cruz, Julia Spanier, Yize Li, Jochen Wilhelm, Huib H Rabouw, Roland Züst, Mihyun Hwang, Philip V'kovski, Hanspeter Stalder, Sabrina Marti, Matthias Habjan, Luisa Cervantes-Barragan, Ruth Elliot, Nadja Karl, Christina Gaughan, Frank J M van Kuppeveld, Robert H Silverman, Markus Keller, Burkhard Ludewig, Cornelia C Bergmann, John Ziebuhr, Susan R Weiss, Ulrich Kalinke, Volker Thiel
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28148787/sars-coronavirus-nucleocapsid-inhibits-type-i-interferon-production-by-interfering-with-trim25-mediated-rig-i-ubiquitination
#5
Yong Hu, Wei Li, Ting Gao, Yan Cui, Yanwen Jin, Ping Li, Qingjun Ma, Xuan Liu, Cheng Cao
: Severe acute respiratory syndrome (SARS) is a respiratory disease caused by a coronavirus (SARS-CoV) that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28148786/neurovirulent-murine-coronavirus-jhm-sd-uses-cellular-zinc-metalloproteases-for-virus-entry-and-cell-cell-fusion
#6
Judith M Phillips, Tom Gallagher, Susan R Weiss
: The coronavirus S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry of the highly neurovirulent MHV strain JHM...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28134071/everyday-dangers-the-impact-infectious-disease-has-on-the-health-of-paramedics-a-scoping-review
#7
Brodie Thomas, Peter O'Meara, Evelien Spelten
BACKGROUND: Paramedics respond to emergency scenes in often uncontrolled settings without being aware of potential risks. This makes paramedicine one of the most dangerous occupations. One of these dangers is the risk of contracting infectious diseases. Research in this area is predominantly focused on compliance in the use of protective equipment, attitudes and perceptions of paramedics, infectious disease policy, and exposure rates to blood and body fluids. The purpose of this scoping review was to determine what is known about the impact of infectious disease on the health of paramedics...
January 30, 2017: Prehospital and Disaster Medicine
https://www.readbyqxmd.com/read/28131392/improving-the-selection-and-development-of-influenza-vaccine-viruses-report-of-a-who-informal-consultation-on-improving-influenza-vaccine-virus-selection-hong-kong-sar-china-18-20-november-2015
#8
Hampson Alan, Barr Ian, Cox Nancy, Donis Ruben O, Hirve Siddhivinayak, Jernigan Daniel, Katz Jacqueline, McCauley John, Motta Fernando, Odagiri Takato, John S Tam, Waddell Anthony, Webby Richard, Ziegler Thedi, Zhang Wenqing
Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies...
January 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28128492/beyond-attachment-roles-of-dc-sign-in-dengue-virus-infection
#9
Ping Liu, Marc Ridilla, Pratik Patel, Laurie Betts, Emily Gallichotte, Lidea Shahidi, Nancy L Thompson, Ken Jacobson
DC-SIGN, a C-type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS, and dengue. A controversial question has been whether DC-SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand-off to another receptor or a co-receptor for internalization. To examine this question, we used four cell types: human immature dendritic cells and NIH3T3 cells expressing either wild type DC-SIGN or two internalization-deficient DC-SIGN mutants, in which either the three cytoplasmic internalization motifs are silenced by alanine substitutions or the cytoplasmic region is truncated...
January 27, 2017: Traffic
https://www.readbyqxmd.com/read/28121202/progress-of-middle-east-respiratory-syndrome-coronavirus-vaccines-a-patent-review
#10
Jiwon Choi, Mi-Gyeong Kim, Yu-Kyoung Oh, Young Bong Kim
Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged as a new pathogen, causing severe complications and a high case fatality rate. No direct treatments are available as yet, highlighting the importance of prevention through suitable vaccination regimes. The viral spike (S) protein has been characterized as a key target antigen for vaccines. In particular, S protein domains have been utilized to produce high titers of neutralizing antibodies. Areas covered: Since the first report of MERS-CoV infection, a limited number of MERS-CoV-specific patents have been filed...
January 25, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28077633/surveillance-of-bat-coronaviruses-in-kenya-identifies-relatives-of-human-coronaviruses-nl63-and-229e-and-their-recombination-history
#11
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
#12
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...
February 15, 2017: 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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