SrasV1, Main, Exploration, bibRecord, 001709

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Identifieur interne : 001709 ( Main/Exploration ); précédent : 001708; suivant : 001710

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Auteurs : Christopher Barton [États-Unis] ; J Calvin Kouokam ; Amanda B. Lasnik ; Oded Foreman ; Alexander Cambon ; Guy Brock ; David C. Montefiori ; Fakhrieh Vojdani ; Alison A. Mccormick ; Barry R. O'Keefe ; Kenneth E. Palmer

Source :

Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2014.

RBID : pubmed:24145548

Descripteurs français

KwdFr :
- Agents antiVIH (pharmacocinétique), Agents antiVIH (sang), Agents antiVIH (usage thérapeutique), Animaux, Antiviraux (pharmacocinétique), Antiviraux (sang), Antiviraux (usage thérapeutique), Cochons d'Inde, Dosage immunologique, Femelle, Lectines végétales (pharmacocinétique), Lectines végétales (sang), Lectines végétales (usage thérapeutique), Protéine d'enveloppe gp120 du VIH (métabolisme), Souris, Souris de lignée BALB C.
MESH :
- métabolisme : Protéine d'enveloppe gp120 du VIH.
- pharmacocinétique : Agents antiVIH, Antiviraux, Lectines végétales.
- sang : Agents antiVIH, Antiviraux, Lectines végétales.
- usage thérapeutique : Agents antiVIH, Antiviraux, Lectines végétales.
- Animaux, Cochons d'Inde, Dosage immunologique, Femelle, Souris, Souris de lignée BALB C.

English descriptors

KwdEn :
- Animals, Anti-HIV Agents (blood), Anti-HIV Agents (pharmacokinetics), Anti-HIV Agents (therapeutic use), Antiviral Agents (blood), Antiviral Agents (pharmacokinetics), Antiviral Agents (therapeutic use), Female, Guinea Pigs, HIV Envelope Protein gp120 (metabolism), Immunoassay, Mice, Mice, Inbred BALB C, Plant Lectins (blood), Plant Lectins (pharmacokinetics), Plant Lectins (therapeutic use).
MESH :
- chemical , blood : Anti-HIV Agents, Antiviral Agents, Plant Lectins.
- chemical , metabolism : HIV Envelope Protein gp120.
- chemical , pharmacokinetics : Anti-HIV Agents, Antiviral Agents, Plant Lectins.
- chemical , therapeutic use : Anti-HIV Agents, Antiviral Agents, Plant Lectins.
- Animals, Female, Guinea Pigs, Immunoassay, Mice, Mice, Inbred BALB C.

Abstract

Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.

DOI: 10.1128/AAC.01407-13
PubMed: 24145548

Affiliations:

Le document en format XML

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<term>Anti-HIV Agents (blood)</term>
<term>Anti-HIV Agents (pharmacokinetics)</term>
<term>Anti-HIV Agents (therapeutic use)</term>
<term>Antiviral Agents (blood)</term>
<term>Antiviral Agents (pharmacokinetics)</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>Female</term>
<term>Guinea Pigs</term>
<term>HIV Envelope Protein gp120 (metabolism)</term>
<term>Immunoassay</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Plant Lectins (blood)</term>
<term>Plant Lectins (pharmacokinetics)</term>
<term>Plant Lectins (therapeutic use)</term>
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<term>Agents antiVIH (sang)</term>
<term>Agents antiVIH (usage thérapeutique)</term>
<term>Animaux</term>
<term>Antiviraux (pharmacocinétique)</term>
<term>Antiviraux (sang)</term>
<term>Antiviraux (usage thérapeutique)</term>
<term>Cochons d'Inde</term>
<term>Dosage immunologique</term>
<term>Femelle</term>
<term>Lectines végétales (pharmacocinétique)</term>
<term>Lectines végétales (sang)</term>
<term>Lectines végétales (usage thérapeutique)</term>
<term>Protéine d'enveloppe gp120 du VIH (métabolisme)</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Antiviral Agents</term>
<term>Plant Lectins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>HIV Envelope Protein gp120</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Antiviral Agents</term>
<term>Plant Lectins</term>
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<term>Antiviral Agents</term>
<term>Plant Lectins</term>
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<term>Antiviraux</term>
<term>Lectines végétales</term>
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<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Agents antiVIH</term>
<term>Antiviraux</term>
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<term>Guinea Pigs</term>
<term>Immunoassay</term>
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<term>Mice, Inbred BALB C</term>
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<term>Cochons d'Inde</term>
<term>Dosage immunologique</term>
<term>Femelle</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections. </div>
</front>
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<name sortKey="Foreman, Oded" sort="Foreman, Oded" uniqKey="Foreman O" first="Oded" last="Foreman">Oded Foreman</name>
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<name sortKey="Palmer, Kenneth E" sort="Palmer, Kenneth E" uniqKey="Palmer K" first="Kenneth E" last="Palmer">Kenneth E. Palmer</name>
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<country name="États-Unis"><region name="Kentucky"><name sortKey="Barton, Christopher" sort="Barton, Christopher" uniqKey="Barton C" first="Christopher" last="Barton">Christopher Barton</name>
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Serveur d'exploration SRAS

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.

Source :

Descripteurs français

English descriptors

Abstract

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

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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