The coelomic fluid of the sea urchin Tripneustes depressus shows antiviral activity against Suid herpesvirus type 1 (SHV-1) and rabies virus (RV)

Salas-Rojas, Mónica; Galvez-Romero, Guillermo; Antón-Palma, Benito; Acevedo, Reynaldo; Blanco-Favéla, Francisco; Aguilar-Setién, Álvaro

doi:10.1016/j.fsi.2013.10.025

Cited by 14 publications

(8 citation statements)

References 26 publications

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“…The viral RdRPs are low-fidelity replicases, having mutation rates of 10 Ϫ4 to 10 Ϫ6 that result in a genetically heterogeneous "quasispecies" population wherein individual viruses differ from the consensus genome sequence at a few random sites (12)(13)(14). Thorough deep-sequencing analysis reveals differences in muta- …”

Section: Importancementioning

confidence: 99%

“…1B) (9, 10). This method appears to be conserved among all positive-stranded RNA viruses based on a consistent "open" active-site conformation seen in polymerase and polymerase-RNA complex structures in the absence of bound NTP, while the "closed" conformation has been seen in poliovirus and norovirus polymerase complexes with RNA and a cognate nucleotide (9, 11).The viral RdRPs are low-fidelity replicases, having mutation rates of 10 Ϫ4 to 10 Ϫ6 that result in a genetically heterogeneous "quasispecies" population wherein individual viruses differ from the consensus genome sequence at a few random sites (12)(13)(14). Thorough deep-sequencing analysis reveals differences in muta- …”

mentioning

confidence: 99%

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Structure-Function Relationships Underlying the Replication Fidelity of Viral RNA-Dependent RNA Polymerases

Campagnola

McDonald

Beaucourt

et al. 2015

J Virol

104

144

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Viral RNA-dependent RNA polymerases are considered to be low-fidelity enzymes, providing high mutation rates that allow for the rapid adaptation of RNA viruses to different host cell environments. Fidelity is tuned to provide the proper balance of virus replication rates, pathogenesis, and tissue tropism needed for virus growth. Using our structures of picornaviral polymerase-RNA elongation complexes, we have previously engineered more than a dozen coxsackievirus B3 polymerase mutations that significantly altered virus replication rates and in vivo fidelity and also provided a set of secondary adaptation mutations after tissue culture passage. Here we report a biochemical analysis of these mutations based on rapid stopped-flow kinetics to determine elongation rates and nucleotide discrimination factors. The data show a spatial separation of fidelity and replication rate effects within the polymerase structure. Mutations in the palm domain have the greatest effects on in vitro nucleotide discrimination, and these effects are strongly correlated with elongation rates and in vivo mutation frequencies, with faster polymerases having lower fidelity. Mutations located at the top of the finger domain, on the other hand, primarily affect elongation rates and have relatively minor effects on fidelity. Similar modulation effects are seen in poliovirus polymerase, an inherently lower-fidelity enzyme where analogous mutations increase nucleotide discrimination. These findings further our understanding of viral RNAdependent RNA polymerase structure-function relationships and suggest that positive-strand RNA viruses retain a unique palm domain-based active-site closure mechanism to fine-tune replication fidelity. IMPORTANCEPositive-strand RNA viruses represent a major class of human and animal pathogens with significant health and economic impacts. These viruses replicate by using a virally encoded RNA-dependent RNA polymerase enzyme that has low fidelity, generating many mutations that allow the rapid adaptation of these viruses to different tissue types and host cells. In this work, we use a structure-based approach to engineer mutations in viral polymerases and study their effects on in vitro nucleotide discrimination as well as virus growth and genome replication fidelity. These results show that mutation rates can be drastically increased or decreased as a result of single mutations at several key residues in the polymerase palm domain, and this can significantly attenuate virus growth in vivo. These findings provide a pathway for developing live attenuated virus vaccines based on engineering the polymerase to reduce virus fitness. P ositive-strand RNA viruses replicate by using virally encoded RNA-dependent RNA polymerases (RdRPs) that provide a direct RNA-to-RNA replication function not found in host cells. The structures of many RdRPs, primarily from picornaviruses, caliciviruses, and flaviviruses, have been solved to reveal a core structure composed of the classic right-hand arrangement of finger, palm, and t...

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Section: Importancementioning

confidence: 99%

mentioning

confidence: 99%

Structure-Function Relationships Underlying the Replication Fidelity of Viral RNA-Dependent RNA Polymerases

Campagnola

McDonald

Beaucourt

et al. 2015

J Virol

104

144

View full text Add to dashboard Cite

show abstract

“…Dang et al, 2011, demonstrated that the total hemolymph and lipophilic extract of the digestive gland from abalone H. laevigata has activity against herpes simplex virus. Salas-Rojas et al, 2014, showed that the coelomic fluid of the sea urchin Tripneustes depressus has antiviral activity against Suid herpesvirus type 1 (SHV-1) and rabies virus (RV). A peptide derived from mastoporan has showed a broad-spectrum antiviral activity against enveloped viruses (Sample et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Antiviral activity of the hemolymph ofPodalia sp and M. albicolis(Lepidoptera: Megalopigydae)

Carvalho

Curti

Oliveira

et al. 2022

Preprint

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Potent antiviral activity against measles, influenza, picornavirus and herpes simplex viruses was observed in the hemolymph of Podalia sp and M. Albicolis (Lepidoptera: Megalopigydae). The antiviral proteins responsible for this activity were isolated by gel filtration chromatography using a gel filtration column system (Superdex 75) and further fractionated using a Resource-Q ion exchange column system. Experiments with the semi-purified protein led to a 128-fold reduction in picornavirus production, 64-fold reduction in measles virus production and a 32-fold reduction in influenza virus replication. qPCR showed a significantly lower level of herpes virus transcription. In addition no citotoxicity and genotoxicity effect was observed for Vero cells, suggesting a very interesting potential antiviral activity.

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“…In addition, highest inhibition against both viruses was observed when coelomic fluid was incubated with them prior to addition of cells, which revelated that coelomic fluid worked directly with the virus and de-stimulated the cell to produce molecules with antiviral effect. The authors suggest that peptides present in coelomic fluid may act by interfering with the virus-cell junction, either via membrane destabilization or receptor blockage ( Salas-Rojas et al, 2014 ).…”

Section: Survey Methodologymentioning

confidence: 99%

Sea urchins: an update on their pharmacological properties

Moreno-García

Salas-Rojas

Fernández-Martínez

et al. 2022

PeerJ

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Sea urchins are a group of benthic invertebrates characterized by having rigid globose bodies, covered in spines, and have an innate immune system that has allowed them to survive in the environment and defend against many pathogens that affect them. They are consumed for their unique flavor, but also for possessing a rich source of bioactive compounds which make them a source for a wide array of medicinal properties. Thus, these may be used to discover and develop new drugs such as anti-bacterials, anti-carcinogenics and anti-virals. Precisely for those reasons, this revision is centered on the known biological activities in various sea urchin species. Recently, the potential pharmacological benefits of nine sea urchin species [Diadema antillarum (Philippi 1845), Echinometra mathaei (de Blainville), Evechinus chloroticus (Valenciennes), Mesocentrotus nudus (Agassiz, 1863), Paracentrotus lividus (Lamarck, 1816), Scaphechinus mirabilis (Agazzis, 1863), Stomopneustes variolaris (Lamarck, 1816), Tripneustes depressus (Agassiz, 1863), and Tripneustes ventricosus (Lamarck, 1816)] have been evaluated. Our work includes a comprehensive review of the anti-fungal, anti-parasitic, anti-inflammatory, hepatoprotective, anti-viral, anti-diabetic, anti-lipidemic, gastro-protective and anti-cardiotoxic effects. Furthermore, we revised the compounds responsible of these pharmacological effects. This work was intended for a broad readership in the fields of pharmacology, drugs and devices, marine biology and aquaculture, fisheries and fish science. Our results suggest that organic extracts, as well as pure compounds obtained from several parts of sea urchin bodies are effective in vitro and in vivo pharmacological models. As such, these properties manifest the potential use of sea urchins to develop emergent active ingredients.

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The coelomic fluid of the sea urchin Tripneustes depressus shows antiviral activity against Suid herpesvirus type 1 (SHV-1) and rabies virus (RV)

Cited by 14 publications

References 26 publications

Structure-Function Relationships Underlying the Replication Fidelity of Viral RNA-Dependent RNA Polymerases

Structure-Function Relationships Underlying the Replication Fidelity of Viral RNA-Dependent RNA Polymerases

Antiviral activity of the hemolymph ofPodalia sp and M. albicolis(Lepidoptera: Megalopigydae)

Sea urchins: an update on their pharmacological properties

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