Guanidine Conditioned Infectivity of Ribonucleic Acid extracted from a Strain of Guanidine-dependent Polio-l-Virus

Loddo, B; Muntoni, Sergio; Spanedda, A; Brotzu, G; Ferrari, W

doi:10.1038/197315a0

Cited by 22 publications

(12 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The existence of viruses, like bacteria, in the three states of drug sensitivity, drug resistance and drug dependence has been demonstrated with HBB by TA~M and Eoo~.as (1963) and also with guanidine (LoDDO et al, 1963). This is of the greatest importance in considering antiviral compounds for use in the prophylaxis or therapy of virus diseases.…”

Section: Discussionmentioning

confidence: 91%

Antiviral action of gliotoxin

McDougall

1969

Archiv f Virusforschung

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 91%

Antiviral action of gliotoxin

McDougall

1969

Archiv f Virusforschung

View full text Add to dashboard Cite

“…GuHCl inhibits the NTPase and RNA helix-unwinding activities of NV NS3. Previous studies have reported that the NTPase and RNA helicase activities of enterovirus 2C ATPase can be inhibited by GuHCl (22,(41)(42)(43)(44)(45), which also inhibits replication of the vRNAs of a number of enteroviruses (46,47). Given the similarity between the consensus motifs in enterovirus 2C ATPase and norovirus NS3, we wanted to examine whether NV NS3 could also be a target for guanidine inhibition.…”

Section: Resultsmentioning

confidence: 99%

“…Virus-encoded RNA-remodeling proteins, particularly helicases, have long been considered valuable targets for antiviral compounds, because they are well conserved within or even across virus families (57). In particular, enterovirus 2C ATPase , another SF3 viral RNA helicase, has been found to be inhibited by ϳ1 mM GuHCl, as is enterovirus replication (22,(42)(43)(44)(45). Using an NV replicon as a model, our studies demonstrated that ϳ1 mM GuHCl can significantly inhibit the replication of HuNoV in cultured human cells with negligible cell toxicity ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities

Hosmillo

Schwanke

et al. 2018

J Virol

View full text Add to dashboard Cite

RNA-remodeling proteins, including RNA helicases and chaperones, act to remodel RNA structures and/or protein-RNA interactions and are required for all processes involving RNAs. Although many viruses encode RNA helicases and chaperones, their activities and their roles in infected cells largely remain elusive. Noroviruses are a diverse group of positive-strand RNA viruses in the family and constitute a significant and potentially fatal threat to human health. Here, we report that the protein NS3 encoded by human norovirus has both ATP-dependent RNA helicase activity that unwinds RNA helices and ATP-independent RNA-chaperoning activity that can remodel structured RNAs and facilitate strand annealing. Moreover, NS3 can facilitate viral RNA synthesis by norovirus polymerase. NS3 may therefore play an important role in norovirus RNA replication. Lastly, we demonstrate that the RNA-remodeling activity of NS3 is inhibited by guanidine hydrochloride, an FDA-approved compound, and, more importantly, that it reduces the replication of the norovirus replicon in cultured human cells. Altogether, these findings are the first to demonstrate the presence of RNA-remodeling activities encoded by and highlight the functional significance of NS3 in the noroviral life cycle. Noroviruses are a diverse group of positive-strand RNA viruses, which annually cause hundreds of millions of human infections and over 200,000 deaths worldwide. For RNA viruses, cellular or virus-encoded RNA helicases and/or chaperones have long been considered to play pivotal roles in viral life cycles. However, neither RNA helicase nor chaperoning activity has been demonstrated to be associated with any norovirus-encoded proteins, and it is also unknown whether norovirus replication requires the participation of any viral or cellular RNA helicases/chaperones. We found that a norovirus protein, NS3, not only has ATP-dependent helicase activity, but also acts as an ATP-independent RNA chaperone. Also, NS3 can facilitate viral RNA synthesis, suggesting the important role of NS3 in norovirus replication. Moreover, NS3 activities can be inhibited by an FDA-approved compound, which also suppresses norovirus replicon replication in human cells, raising the possibility that NS3 could be a target for antinoroviral drug development.

show abstract

“…Several guanidine derivatives have nevertheless been synthesized with more potent antiviral activity (Bucknall et al, 1973). Soon after the discovery of guanidine as an antiviral agent (Rightsel et al, 1961), poliovirus mutants resistant to or dependent on guanidine were described (Loddo et al, 1963;Nakano et al, 1963). The picornaviruses inhibited by guanidine are poliovirus, rhinovirus and FMDV, whereas EMC virus is resistant to the compound (Caliguiri and Tamm, 1973;Tershak et al, 1982).…”

Section: Cellular Membranes and Picornavirus Rna Synthesismentioning

confidence: 99%

Picornavirus inhibitors

Carrasco

1994

Pharmacology & Therapeutics

View full text Add to dashboard Cite

Picornaviruses are among the best understood animal viruses in molecular terms. A number of important human and animal pathogens are members of the Picornaviridae family. The genome organization, the different steps of picornavirus growth and numerous compounds that have been reported as inhibitors of picornavirus functions are reviewed. The picornavirus particles and several agents that interact with them have been solved at atomic resolution, leading to computer-assisted drug design. Picornavirus inhibitors are useful in aiding a better understanding of picornavirus biology. In addition, some of them are promising therapeutic agents. Clinical efficacy of agents that bind to picornavirus particles has already been demonstrated.

show abstract

Guanidine Conditioned Infectivity of Ribonucleic Acid extracted from a Strain of Guanidine-dependent Polio-l-Virus

Cited by 22 publications

References 1 publication

Antiviral action of gliotoxin

Antiviral action of gliotoxin

Human Norovirus NS3 Has RNA Helicase and Chaperoning Activities

Picornavirus inhibitors

Contact Info

Product

Resources

About