A newly developed immunofluorescent assay for determining the Pichinde virus-inhibitory effects of selected nucleoside analogues

Burns, N. J.; Barnett, Bill B.; Huffman, John H.; Dawson, Marcia I.; Sidwell, Robert W.; Clercq, Erik De; Kende, Meir

doi:10.1016/0166-3542(88)90017-4

Cited by 9 publications

(2 citation statements)

References 16 publications

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“…With respect to Lassa fever, chemotherapy with ribavirin is the preferred treatment, but with a high level of undesirable secondary reactions (McCormick et al, 1986;McKee et al, 1988). Other nucleoside analogues were assayed in vitro and in vivo, but without successful results (Huggins et al, 1984;Burns et al, 1988;Andrei & de Clercq, 1990;Smee et al, 1993;Guillerm et al, 2003;Uckun et al, 2004). Thus, the development and evaluation of effective agents directed to new targets in the viral cycle constitute a necessary approach for arenavirus chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

Garcı́a

Djavani

Topisirović

et al. 2006

Journal of General Virology

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Several disulfide-based and azoic compounds have shown antiviral and virucidal properties against arenaviruses in virus yield-inhibition and inactivation assays, respectively. The most effective virucidal agent, the aromatic disulfide NSC20625, was able to inactivate two strains of the prototype arenavirus species Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained the biological functions of the virion envelope glycoproteins in virus binding and uptake, but were unable to perform viral RNA replication. Furthermore, in inactivated virions, the electrophoretic profile of the Z protein was altered when analysed under non-reducing conditions, whereas the patterns of the proteins NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with the virucidal agents induced unfolding and oligomerization of Z to high-molecular-mass aggregates, probably due to metal-ion ejection and the formation of intermolecular disulfide bonds through the cysteine residues of the Z RING finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells without affecting other cellular RING-motif proteins, such as the promyelocytic leukaemia protein PML. Altogether, the investigations described here illustrate the potential of the Z protein as a promising target for therapy and the prospects of the Z-reactive compounds to prevent arenavirus dissemination. INTRODUCTIONThe family Arenaviridae comprises several virus species included in a single genus, Arenavirus (Salvato et al., 2005). Based on geographical distribution, antigenic cross-reactivity and phylogenetic analyses, the genus is divided into two groups (Wulff et al., 1978;Howard, 1993;Clegg, 2002;Charrel et al., 2003): (i) the Old World group, including four African arenaviruses and Lymphocytic choriomeningitis virus (LCMV), the prototypic and most widely distributed species, and (ii) the New World group, which comprises 18 viruses distributed in South and North America. Several arenaviruses are human pathogens: LCMV has teratogenic effects and can cause aseptic meningitis, whereas five members of the family, Junín virus (JUNV), Machupo virus, Guanarito virus, Sabiá virus and Lassa virus (LASV), can cause severe haemorrhagic fever (HF) (McCormick & Fisher-Hoch, 2002;Peters, 2002). The danger of arenaviruses for human health, their increased emergence and the absence of either effective chemotherapy or approved vaccines support their consideration as potential agents of bioterrorism (Damonte & Coto, 2002;Rotz et al., 2002).The virions contain two single-stranded RNA molecules known as L (large) and S (small), arranged as helical nucleocapsids and enclosed in a lipid envelope. Each genome segment presents an ambisense coding strategy, with two genes in opposite orientations and separated by an intergenic non-coding region (Auperin et al., 1984). The L fragment encodes the RNA-dependent RNA polymerase L at its 39 end from an antigenome-sense mRNA and a zincbinding protein named Z at the 59 end from a genome-sense mRNA (Salvato & Sh...

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Section: Discussionmentioning

confidence: 99%

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

Garcı́a

Djavani

Topisirović

et al. 2006

Journal of General Virology

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“…Our study, to the best of our knowledge, is the first to demonstrate the antiretroviral activity of formycin A. Many previous studies identified the activity of 3-deazauridine against riboviruses (20)(21)(22)(23)(24)(25)(26) and retroviruses (23,27). Interestingly, 3-deazauridine was previously observed to potentiate the anti-HIV-1 activity of 3TC and dideoxycytosine (28).…”

Section: Discussionmentioning

confidence: 85%

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Dapp

Bonnac

Patterson

et al. 2014

J Virol

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Reverse transcription is an important early step in retrovirus replication and is a key point targeted by evolutionarily conserved host restriction factors (e.g., APOBEC3G, SamHD1). Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target of antiretroviral drugs, and concerns regarding drug resistance and off-target effects have led to continued efforts for identifying novel approaches to targeting HIV-1 RT. Several observations, including those obtained from monocytederived macrophages, have argued that ribonucleotides and their analogs can, intriguingly, impact reverse transcription. For example, we have previously demonstrated that 5-azacytidine has its greatest antiviral potency during reverse transcription by enhancement of G-to-C transversion mutations. In the study described here, we investigated a panel of ribonucleoside analogs for their ability to affect HIV-1 replication during the reverse transcription process. We discovered five ribonucleosides-8-azaadenosine, formycin A, 3-deazauridine, 5-fluorocytidine, and 2=-C-methylcytidine-that possess anti-HIV-1 activity, and one of these (i.e., 3-deazauridine) has a primary antiviral mechanism that involves increased HIV-1 mutational loads, while quantitative PCR analysis determined that the others resulted in premature chain termination. Taken together, our findings provide the first demonstration of a series of ribonucleoside analogs that can target HIV-1 reverse transcription with primary antiretroviral mechanisms that include premature termination of viral DNA synthesis or enhanced viral mutagenesis.

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Antiviral immunotoxins: antibody-mediated delivery of gelonin inhibits Pichinde virus replication in vitro

Barnett

Burns²,

Park

et al. 1991

Antiviral Research

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A newly developed immunofluorescent assay for determining the Pichinde virus-inhibitory effects of selected nucleoside analogues

Cited by 9 publications

References 16 publications

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

Discovery of Novel Ribonucleoside Analogs with Activity against Human Immunodeficiency Virus Type 1

Antiviral immunotoxins: antibody-mediated delivery of gelonin inhibits Pichinde virus replication in vitro

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