coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus.coronaviruses are a family of enveloped, single-stranded, positive-strand rna viruses classified within the nidovirales order. this coronavirus family consists of pathogens of many animal species and of humans, including the recently isolated severe acute respiratory syndrome coronavirus (sars-cov). this review is divided into two main parts; the first concerns the animal coronaviruses and their pathogenesis, with an emphasis on the functions of individual viral genes, and the second discusses t ...200516339739
sybr green real-time reverse transcription-polymerase chain reaction assay for the generic detection of coronaviruses.coronaviruses are etiologic agents of respiratory and enteric diseases in humans and in animals. in this study, a one-step real-time reverse transcription-polymerase chain reaction (rt-pcr) assay based on sybr green chemistry and degenerate primers was developed for the generic detection of coronaviruses. the primers, designed in the open reading frame 1b, enabled the detection of 32 animal coronaviruses including strains of canine coronavirus, feline coronavirus, transmissible gastroenteritis v ...200716941059
structures of the n- and c-terminal domains of mhv-a59 nucleocapsid protein corroborate a conserved rna-protein binding mechanism in coronavirus.coronaviruses are the causative agent of respiratory and enteric diseases in animals and humans. one example is sars, which caused a worldwide health threat in 2003. in coronaviruses, the structural protein n (nucleocapsid protein) associates with the viral rna to form the filamentous nucleocapsid and plays a crucial role in genome replication and transcription. the structure of n-terminal domain of mhv n protein also implicated its specific affinity with transcriptional regulatory sequence (trs ...201021203940
atp1a1-mediated src signaling inhibits coronavirus entry into host addition to transporting ions, the multisubunit na(+),k(+)-atpase also functions by relaying cardiotonic steroid (cts)-binding-induced signals into cells. in this study, we analyzed the role of na(+),k(+)-atpase and, in particular, of its atp1a1 α subunit during coronavirus (cov) infection. as controls, the vesicular stomatitis virus (vsv) and influenza a virus (iav) were included. using gene silencing, the atp1a1 protein was shown to be critical for infection of cells with murine hepatitis v ...201525653449
murine hepatitis virus nsp14 exoribonuclease activity is required for resistance to innate immunity.coronaviruses (covs) are positive-sense rna viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. covs encode several innate immune antagonists that counteract the host innate immune response to facilitate efficient viral replication. cov nonstructural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (exon), which performs a proofreading function and is required for high-fidelity replication. outside of the ordernidov ...201829046453
coronavirus susceptibility to the antiviral remdesivir (gs-5734) is mediated by the viral polymerase and the proofreading exoribonuclease.emerging coronaviruses (covs) cause severe disease in humans, but no approved therapeutics are available. the cov nsp14 exoribonuclease (exon) has complicated development of antiviral nucleosides due to its proofreading activity. we recently reported that the nucleoside analogue gs-5734 (remdesivir) potently inhibits human and zoonotic covsin vitroand in a severe acute respiratory syndrome coronavirus (sars-cov) mouse model. however, studies with gs-5734 have not reported resistance associated w ...201829511076
genomic modeling as an approach to identify surrogates for use in experimental validation of sars-cov-2 and hunov inactivation by uv-c treatment.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) is responsible for the covid-19 pandemic that continues to pose significant public health concerns. while research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. ultraviolet light (uv-c) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. in this study, we developed a pyrimidine din ...202033133042
receptor tyrosine kinase inhibitors block proliferation of tgev mainly through p38 mitogen-activated protein kinase pathways.emerging coronaviruses (covs) primarily cause severe gastroenteric or respiratory diseases in humans and animals, and no approved therapeutics are currently available. here, a9, a receptor tyrosine kinase inhibitor (rtki) of the tyrphostin class, is identified as a robust inhibitor of transmissible gastroenteritis virus (tgev) infection in cell-based assays. moreover, a9 exhibited potent antiviral activity against the replication of various covs, including murine hepatitis virus (mhv), porcine e ...202031751591
small-molecule antiviral β-d-n4-hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance.coronaviruses (covs) have emerged from animal reservoirs to cause severe and lethal disease in humans, but there are currently no fda-approved antivirals to treat the infections. one class of antiviral compounds, nucleoside analogues, mimics naturally occurring nucleosides to inhibit viral replication. while these compounds have been successful therapeutics for several viral infections, mutagenic nucleoside analogues, such as ribavirin and 5-fluorouracil, have been ineffective at inhibiting covs ...201931578288
interplay between coronavirus, a cytoplasmic rna virus, and nonsense-mediated mrna decay pathway.coronaviruses (covs), including severe acute respiratory syndrome cov and middle east respiratory syndrome cov, are enveloped rna viruses that carry a large positive-sense single-stranded rna genome and cause a variety of diseases in humans and domestic animals. very little is known about the host pathways that regulate the stability of cov mrnas, which carry some unusual features. nonsense-mediated decay (nmd) is a eukaryotic rna surveillance pathway that detects mrnas harboring aberrant featur ...201830297408
chlordecone potentiates auto-immune hepatitis and promotes brain entry of mhv3 during viral hepatitis in mouse models.chlordecone is an organochlorine used in the 1970's as a pesticide in banana plantations. it has a long half-life in the soil and can potentially contaminate humans and animals through food. chlordecone targets, and mainly accumulates in, the liver, leading to hepatomegaly and neurological signs in mammals. chlordecone does not cause liver injuries or any inflammation by itself at low doses, but it can potentiate the hepatotoxic effects of other chemicals and drugs. we studied the impact of chlo ...201830287270
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