Inhibition of murine coronavirus RNA synthesis by hydroxyguanidine derivatives

Keck, James; Pou-Hsiung, Wang; Lien, Eric J.; Lai, Michael M. C.

doi:10.1016/0168-1702(89)90069-5

Cited by 6 publications

(2 citation statements)

References 17 publications

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“…Attempts which have been most successful include immunotherapy with various combinations of interferon (14,19,60) or with neutralizing antibodies or antibody fragments (41,62). Limited data indicate mixed anticoronaviral activity for nucleoside analogs including riba- virin (11,16,18,35,44,59,71,78,82) and an assortment of other small molecules (8,10,13,55,69,80). Corticosteroid treatment has proved generally ineffective against coronaviruses (3,4).…”

Section: Discussionmentioning

confidence: 99%

Antisense Morpholino-Oligomers Directed against the 5′ End of the Genome Inhibit Coronavirus Proliferation and Growth†

Neuman

Stein

Kroeker

et al. 2004

J Virol

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Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers. Conjugated and unconjugated oligomers were tested to determine sequence-specific antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus (MHV). Specific antisense activity designed to block translation of the viral replicase polyprotein was first confirmed by reduction of luciferase expression from a target sequence-containing reporter construct in both cell-free and transfected cell culture assays. Peptide-conjugated morpholino-oligomers exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer administered at micromolar concentrations was delivered to >80% of cells and inhibited virus titers 10-to 100-fold in a sequence-specific and dose-responsive manner. In addition, targeted viral protein synthesis, plaque diameter, and cytopathic effect were significantly reduced. Inhibition of virus infectivity by peptide-conjugated morpholino was comparable to the antiviral activity of the aminoglycoside hygromycin B used at a concentration fivefold higher than the oligomer. These results suggest that this composition of antisense compound has therapeutic potential for control of coronavirus infection.Coronaviruses are medically and economically important pathogens of humans, livestock, and birds. Coronavirus infections cause a wide range of symptoms, including upper respiratory illness, gastroenteritis, myocarditis, nephritis, central nervous system demyelination, encephalitis, hepatitis, and peritonitis, and can have a debilitating effect on the host immune system, leading to secondary microbial infection. In humans a coronavirus infection marked by aerosol transmissibility and a high degree of immunopathology-related mortality has been linked with the outbreak of severe acute respiratory syndrome (52, 64). Other human coronaviruses cause approximately one-third of all cases of common colds (20,29,56

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Section: Discussionmentioning

confidence: 99%

Antisense Morpholino-Oligomers Directed against the 5′ End of the Genome Inhibit Coronavirus Proliferation and Growth†

Neuman

Stein

Kroeker

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…For the purpose of preparing viral RNA template during cDNA cloning, FECV was grown in whole feline embryo (WFE) cells (Harbour et al, 1991) in the presence of 1 Ixg/ml of actinomycin D. This concentration of actinomycin D has been reported to have a minimal effect on the replication of other coronaviruses [FIPV, de Groot et al (1987); bovine coronavirus, Keck et al (1988); rat coronavirus, Parker et al (1970); mouse hepatitis virus (MHV), Keck et al (1989), Spaan et al (1981) and Malluci (1965); infectious bronchitis virus (IBV), Lomniczi & Kennedy (1977); human coronavirus (HCV) 229E, Schreiber et at. (1989)].…”

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confidence: 99%