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SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

Identifieur interne : 001E20 ( Main/Exploration ); précédent : 001E19; suivant : 001E21

SP-303, an antiviral oligomeric proanthocyanidin from the latex of Croton lechleri (Sangre de Drago).

Auteurs : R. Ubillas [États-Unis] ; S. D. Jolad [États-Unis] ; R. C. Bruening [États-Unis] ; M. R. Kernan [États-Unis] ; S. R. King [États-Unis] ; D. F. Sesin [États-Unis] ; M. Barrett [États-Unis] ; C. A. Stoddart [États-Unis] ; T. Flaster [États-Unis] ; J. Kuo [États-Unis] ; F. Ayala [États-Unis] ; E. Meza [États-Unis] ; M. Casta El [États-Unis] ; D. Mcmeekin [États-Unis] ; E. Rozhon [États-Unis] ; M. S. Tempesta [États-Unis] ; D. Barnard [États-Unis] ; J. Huffman [États-Unis] ; D. Smee [États-Unis] ; R. Sidwell [États-Unis] ; K. Soike [États-Unis] ; A. Brazier [États-Unis] ; S. Safrin [États-Unis] ; R. Orlando [Japon] ; P. T. M. Kenny [Japon] ; N. Berova [États-Unis, Bulgarie] ; K. Nakanishi [États-Unis]

Source :

RBID : ISTEX:7A7B9DC7F79C3BFB0C49C0022E453CAE3A580488

English descriptors

Abstract

Summary: SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent.

Url:
DOI: 10.1016/S0944-7113(11)80026-7


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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<term>Acyclovir</term>
<term>Adsorption</term>
<term>Aerosol inhalation</term>
<term>Agents chemo</term>
<term>Amazonian ecuador</term>
<term>Animal models</term>
<term>Antimicrob</term>
<term>Antiviral</term>
<term>Antiviral activities</term>
<term>Antiviral activity</term>
<term>Antiviral agents</term>
<term>Antiviral assay</term>
<term>Antiviral compounds</term>
<term>Antiviral effect</term>
<term>Antiviral mechanism</term>
<term>Antiviral research</term>
<term>Aqueous acetone</term>
<term>Assay</term>
<term>Atcc</term>
<term>Atom bombardment mass spectrum</term>
<term>Average chain length</term>
<term>Average formula</term>
<term>Baylor</term>
<term>Baylor university</term>
<term>Binding studies</term>
<term>Boca raton</term>
<term>Carboxymethyl cellulose</term>
<term>Catechin</term>
<term>Cell culture</term>
<term>Cell culture medium</term>
<term>Cell lines</term>
<term>Cellular viability</term>
<term>Central america</term>
<term>Chain lengths</term>
<term>Chemical shifts</term>
<term>Circular dichroism spectra</term>
<term>Clin signs</term>
<term>Clinical chemistry parameters</term>
<term>Clinical signs</term>
<term>Cofan indians</term>
<term>Control animals</term>
<term>Cotton rats</term>
<term>Croton</term>
<term>Croton lechleri</term>
<term>Croton species</term>
<term>Cytoplasmic vacuoles</term>
<term>Cytotoxic</term>
<term>Cytotoxic endpoint</term>
<term>Dark discoloration</term>
<term>Determ ined</term>
<term>Different concentrations</term>
<term>Dos</term>
<term>Dosage</term>
<term>Dosage group</term>
<term>Dosage groups</term>
<term>Dosage level</term>
<term>Dosage levels</term>
<term>Dosage route</term>
<term>Dosing</term>
<term>Dosing period</term>
<term>Dosing study</term>
<term>Drago</term>
<term>Ecuador</term>
<term>Edso</term>
<term>Edso values</term>
<term>Elemental analyses</term>
<term>Endpoint</term>
<term>Epicatechin</term>
<term>Estudio preliminar</term>
<term>Ethyl acetate</term>
<term>Experimental conditions</term>
<term>Experimental parameters</term>
<term>Experimental range</term>
<term>Fabms</term>
<term>Female rats</term>
<term>Final product</term>
<term>Flavanoid units</term>
<term>Flow rate</term>
<term>Foreskin fibroblast</term>
<term>Gallocatechin</term>
<term>Genital lesions</term>
<term>Genus croton</term>
<term>Grain size</term>
<term>Green monkey</term>
<term>Guinea</term>
<term>Guinea pigs</term>
<term>Hepatitis</term>
<term>Herpes</term>
<term>Herpes simplex virus type</term>
<term>Herpes viruses</term>
<term>High dose</term>
<term>High dose females</term>
<term>High vacuum</term>
<term>Highest concentration</term>
<term>Histiocyte</term>
<term>Incubation period</term>
<term>Indigenous names</term>
<term>Individual units</term>
<term>Influenza</term>
<term>Influenza virus</term>
<term>Influenza virus infection</term>
<term>Inhalation</term>
<term>Inhalation route</term>
<term>Inhibitory</term>
<term>Inhibitory activity</term>
<term>Inhibitory concentration</term>
<term>Inhibitory endpoints</term>
<term>Intraperitoneal administration</term>
<term>Intravenous</term>
<term>Intravenous administration</term>
<term>Large body</term>
<term>Latex</term>
<term>Lechleri</term>
<term>Lesion</term>
<term>Loglo tcid</term>
<term>Magic bullet</term>
<term>Management plans</term>
<term>Mass spectra</term>
<term>Measles viru</term>
<term>Mesenteric lymph nodes</term>
<term>Mglkg</term>
<term>Mglkg infusion</term>
<term>Mobile phase</term>
<term>Molecular weight</term>
<term>Molecular weight range</term>
<term>Monomer</term>
<term>Monomeric units</term>
<term>Natural products</term>
<term>Nucleoside analogues</term>
<term>Oligomer</term>
<term>Oral administration</term>
<term>Oral dosage</term>
<term>Oral gavage</term>
<term>Other studies</term>
<term>Parainfluenza virus type</term>
<term>Peak apex</term>
<term>Permeation</term>
<term>Permeation chromatogram</term>
<term>Permeation chromatography</term>
<term>Phosphate buffer</term>
<term>Photo diode array detector</term>
<term>Placebo</term>
<term>Placebo groups</term>
<term>Plaque</term>
<term>Plaque neutralization assay</term>
<term>Plaque reduction assay</term>
<term>Plasma membrane</term>
<term>Polymer</term>
<term>Polymer laboratories</term>
<term>Polymeric proanthocyanidins</term>
<term>Polystyrene standards</term>
<term>Positive controls</term>
<term>Proanthocyanidin</term>
<term>Proanthocyanidin oligomer</term>
<term>Proanthocyanidin polymer</term>
<term>Proanthocyanidin polymers</term>
<term>Proanthocyanidins</term>
<term>Procyanidinlprodelphinidin units</term>
<term>Prophylactic regimen</term>
<term>Prophylactic study</term>
<term>Proton assignments</term>
<term>Pulmonary titers</term>
<term>Rat</term>
<term>Raven press</term>
<term>Recovery animals</term>
<term>Recovery period</term>
<term>Regimen</term>
<term>Relative stereochemistry</term>
<term>Replication</term>
<term>Respiratory syncytial virus</term>
<term>Respiratory viruses</term>
<term>Reticuloendothelial system</term>
<term>Rhinovirus</term>
<term>Ribavirin</term>
<term>Sangre</term>
<term>Second edition fields</term>
<term>Selectivity index</term>
<term>Sephadex column</term>
<term>Shaman</term>
<term>Shaman pharmaceuticals</term>
<term>Significant cornpared</term>
<term>Significant efficacy</term>
<term>Significant findings</term>
<term>Significant reductions</term>
<term>Simplex</term>
<term>Single dose toxicity studies</term>
<term>Single study</term>
<term>Small amount</term>
<term>Small particle aerosol</term>
<term>Small quantities</term>
<term>Source species</term>
<term>Southern brazil</term>
<term>Southern research institute</term>
<term>Species study</term>
<term>Specific rotation</term>
<term>Specific rotation data</term>
<term>Spectral data</term>
<term>Stereochemistries</term>
<term>Stereochemistry</term>
<term>Syncytial</term>
<term>Synt hesis</term>
<term>Tannin</term>
<term>Terminal unit</term>
<term>Terminal units</term>
<term>Test compound</term>
<term>Thymidine kinase</term>
<term>Time curve</term>
<term>Titer</term>
<term>Topical application</term>
<term>Topical treatment</term>
<term>Toxicity</term>
<term>Ubillas</term>
<term>Uninfected cells</term>
<term>Utah state university</term>
<term>Vacuum oven</term>
<term>Vaginal infection</term>
<term>Vaginal wash</term>
<term>Vira</term>
<term>Viral</term>
<term>Viral adsorption period</term>
<term>Viral attachment</term>
<term>Viral diseases</term>
<term>Viral effect</term>
<term>Viral envelope</term>
<term>Viral families</term>
<term>Viral infection</term>
<term>Viral particle</term>
<term>Viral replication</term>
<term>Viral titers</term>
<term>Virucidal test</term>
<term>Virus</term>
<term>Virus replication</term>
<term>Weight distribution</term>
<term>Weight loss</term>
<term>Whittaker atcc</term>
<term>Wound healing agent</term>
<term>Wyde</term>
</keywords>
</textClass>
<langUsage>
<language ident="en">en</language>
</langUsage>
</profileDesc>
</teiHeader>
<front>
<div type="abstract">Summary: SP-303, a large proanthocyanidin oligomer isolated from the latex of the plant species Croton lechleri (Eupborbiaceae) has demonstrated broad activity against a variety of DNA and RNA viruses. In cell culture, SP-303 exhibits potent activity against isolates and laboratory strains of respiratory syncytial virus (RSV), influenza A virus (FLU-A) and parainfluenza virus (PIV). Parallel assays of SP-303 and ribavirin showed comparable activity against these viruses. SP-303 also exhibits significant inhibitory activity against herpesvirus (HSV) types 1 and 2, including herpesviruses resistant to acyclovir and foscarnet. Inhibition was also observed against hepatitis A and B viruses. The antiviral mechanism of SP-303 seems to derive from its direct binding to components of the viral envelope, resulting in inhibition of viral attachment and penetration of the plasma membrane. Antiviral effects of SP-303 were measured by three distinct methods: CPE, MTT and precursor uptake/incorporation. Cytotoxicity endpoints were markedly greater than the respective antiviral endpoints. SP-303 exhibited activity in RSV-infected cotton rats and African green monkeys, PIV-3-infected cotton rats, HSV-2 infected mice and guinea pigs and FLU-A-infected mice. The most successful routes of SP-303 administration for producing efficacy were: topical application to HSV-2- genital lesions in mice and guinea pigs, aerosol inhalation to FLU-A-infected mice and PIV-3-infected cotton rats, and oral dosage to RSV-infected cotton rats. A variety of toxicological evaluations demonstrated the safety of SP-303, particularly orally, which was predictable, since condensed tannins are a common dietary component. It is notable that the larger proanthocyanidins as a class have high antiviral activity, whereas most of the monomers are inactive. Clinical trials are ongoing to evaluate SP-303 as a therapeutic antiviral agent.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>Bulgarie</li>
<li>Japon</li>
<li>États-Unis</li>
</country>
<region>
<li>Alabama</li>
<li>Californie</li>
<li>Louisiane</li>
<li>Sofia-ville (oblast)</li>
<li>Utah</li>
<li>État de New York</li>
</region>
<settlement>
<li>New York</li>
<li>Sofia</li>
</settlement>
<orgName>
<li>Université Columbia</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Californie">
<name sortKey="Ubillas, R" sort="Ubillas, R" uniqKey="Ubillas R" first="R." last="Ubillas">R. Ubillas</name>
</region>
<name sortKey="Ayala, F" sort="Ayala, F" uniqKey="Ayala F" first="F." last="Ayala">F. Ayala</name>
<name sortKey="Barnard, D" sort="Barnard, D" uniqKey="Barnard D" first="D." last="Barnard">D. Barnard</name>
<name sortKey="Barrett, M" sort="Barrett, M" uniqKey="Barrett M" first="M." last="Barrett">M. Barrett</name>
<name sortKey="Berova, N" sort="Berova, N" uniqKey="Berova N" first="N." last="Berova">N. Berova</name>
<name sortKey="Brazier, A" sort="Brazier, A" uniqKey="Brazier A" first="A." last="Brazier">A. Brazier</name>
<name sortKey="Bruening, R C" sort="Bruening, R C" uniqKey="Bruening R" first="R. C." last="Bruening">R. C. Bruening</name>
<name sortKey="Casta El, M" sort="Casta El, M" uniqKey="Casta El M" first="M." last="Casta El">M. Casta El</name>
<name sortKey="Flaster, T" sort="Flaster, T" uniqKey="Flaster T" first="T." last="Flaster">T. Flaster</name>
<name sortKey="Huffman, J" sort="Huffman, J" uniqKey="Huffman J" first="J." last="Huffman">J. Huffman</name>
<name sortKey="Jolad, S D" sort="Jolad, S D" uniqKey="Jolad S" first="S. D." last="Jolad">S. D. Jolad</name>
<name sortKey="Kernan, M R" sort="Kernan, M R" uniqKey="Kernan M" first="M. R." last="Kernan">M. R. Kernan</name>
<name sortKey="King, S R" sort="King, S R" uniqKey="King S" first="S. R." last="King">S. R. King</name>
<name sortKey="Kuo, J" sort="Kuo, J" uniqKey="Kuo J" first="J." last="Kuo">J. Kuo</name>
<name sortKey="Mcmeekin, D" sort="Mcmeekin, D" uniqKey="Mcmeekin D" first="D." last="Mcmeekin">D. Mcmeekin</name>
<name sortKey="Meza, E" sort="Meza, E" uniqKey="Meza E" first="E." last="Meza">E. Meza</name>
<name sortKey="Nakanishi, K" sort="Nakanishi, K" uniqKey="Nakanishi K" first="K." last="Nakanishi">K. Nakanishi</name>
<name sortKey="Rozhon, E" sort="Rozhon, E" uniqKey="Rozhon E" first="E." last="Rozhon">E. Rozhon</name>
<name sortKey="Safrin, S" sort="Safrin, S" uniqKey="Safrin S" first="S." last="Safrin">S. Safrin</name>
<name sortKey="Sesin, D F" sort="Sesin, D F" uniqKey="Sesin D" first="D. F." last="Sesin">D. F. Sesin</name>
<name sortKey="Sidwell, R" sort="Sidwell, R" uniqKey="Sidwell R" first="R." last="Sidwell">R. Sidwell</name>
<name sortKey="Smee, D" sort="Smee, D" uniqKey="Smee D" first="D." last="Smee">D. Smee</name>
<name sortKey="Soike, K" sort="Soike, K" uniqKey="Soike K" first="K." last="Soike">K. Soike</name>
<name sortKey="Stoddart, C A" sort="Stoddart, C A" uniqKey="Stoddart C" first="C. A." last="Stoddart">C. A. Stoddart</name>
<name sortKey="Tempesta, M S" sort="Tempesta, M S" uniqKey="Tempesta M" first="M. S." last="Tempesta">M. S. Tempesta</name>
<name sortKey="Tempesta, M S" sort="Tempesta, M S" uniqKey="Tempesta M" first="M. S." last="Tempesta">M. S. Tempesta</name>
</country>
<country name="Japon">
<noRegion>
<name sortKey="Orlando, R" sort="Orlando, R" uniqKey="Orlando R" first="R." last="Orlando">R. Orlando</name>
</noRegion>
<name sortKey="Kenny, P T M" sort="Kenny, P T M" uniqKey="Kenny P" first="P. T. M." last="Kenny">P. T. M. Kenny</name>
</country>
<country name="Bulgarie">
<region name="Sofia-ville (oblast)">
<name sortKey="Berova, N" sort="Berova, N" uniqKey="Berova N" first="N." last="Berova">N. Berova</name>
</region>
</country>
</tree>
</affiliations>
</record>

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