Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.
Identifieur interne : 001113 ( PubMed/Corpus ); précédent : 001112; suivant : 001114Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.
Auteurs : Christopher Barton ; 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. PalmerSource :
- Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2014.
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
Links to Exploration step
pubmed:24145548Le document en format XML
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Lasnik</name></author><author><name sortKey="Foreman, Oded" sort="Foreman, Oded" uniqKey="Foreman O" first="Oded" last="Foreman">Oded Foreman</name></author><author><name sortKey="Cambon, Alexander" sort="Cambon, Alexander" uniqKey="Cambon A" first="Alexander" last="Cambon">Alexander Cambon</name></author><author><name sortKey="Brock, Guy" sort="Brock, Guy" uniqKey="Brock G" first="Guy" last="Brock">Guy Brock</name></author><author><name sortKey="Montefiori, David C" sort="Montefiori, David C" uniqKey="Montefiori D" first="David C" last="Montefiori">David C. Montefiori</name></author><author><name sortKey="Vojdani, Fakhrieh" sort="Vojdani, Fakhrieh" uniqKey="Vojdani F" first="Fakhrieh" last="Vojdani">Fakhrieh Vojdani</name></author><author><name sortKey="Mccormick, Alison A" sort="Mccormick, Alison A" uniqKey="Mccormick A" first="Alison A" last="Mccormick">Alison A. 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Lasnik</name></author><author><name sortKey="Foreman, Oded" sort="Foreman, Oded" uniqKey="Foreman O" first="Oded" last="Foreman">Oded Foreman</name></author><author><name sortKey="Cambon, Alexander" sort="Cambon, Alexander" uniqKey="Cambon A" first="Alexander" last="Cambon">Alexander Cambon</name></author><author><name sortKey="Brock, Guy" sort="Brock, Guy" uniqKey="Brock G" first="Guy" last="Brock">Guy Brock</name></author><author><name sortKey="Montefiori, David C" sort="Montefiori, David C" uniqKey="Montefiori D" first="David C" last="Montefiori">David C. Montefiori</name></author><author><name sortKey="Vojdani, Fakhrieh" sort="Vojdani, Fakhrieh" uniqKey="Vojdani F" first="Fakhrieh" last="Vojdani">Fakhrieh Vojdani</name></author><author><name sortKey="Mccormick, Alison A" sort="Mccormick, Alison A" uniqKey="Mccormick A" first="Alison A" last="Mccormick">Alison A. Mccormick</name></author><author><name sortKey="O Keefe, Barry R" sort="O Keefe, Barry R" uniqKey="O Keefe B" first="Barry R" last="O'Keefe">Barry R. O'Keefe</name></author><author><name sortKey="Palmer, Kenneth E" sort="Palmer, Kenneth E" uniqKey="Palmer K" first="Kenneth E" last="Palmer">Kenneth E. Palmer</name></author></analytic><series><title level="j">Antimicrobial agents and chemotherapy</title><idno type="eISSN">1098-6596</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><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></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></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-HIV Agents</term><term>Antiviral Agents</term><term>Plant Lectins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Guinea Pigs</term><term>Immunoassay</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords></textClass></profileDesc></teiHeader><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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24145548</PMID><DateCompleted><Year>2014</Year><Month>09</Month><Day>18</Day></DateCompleted><DateRevised><Year>2018</Year><Month>11</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1098-6596</ISSN><JournalIssue CitedMedium="Internet"><Volume>58</Volume><Issue>1</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>Antimicrobial agents and chemotherapy</Title><ISOAbbreviation>Antimicrob. Agents Chemother.</ISOAbbreviation></Journal><ArticleTitle>Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models.</ArticleTitle><Pagination><MedlinePgn>120-7</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1128/AAC.01407-13</ELocationID><Abstract><AbstractText>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. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Barton</LastName><ForeName>Christopher</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kouokam</LastName><ForeName>J Calvin</ForeName><Initials>JC</Initials></Author><Author ValidYN="Y"><LastName>Lasnik</LastName><ForeName>Amanda B</ForeName><Initials>AB</Initials></Author><Author ValidYN="Y"><LastName>Foreman</LastName><ForeName>Oded</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Cambon</LastName><ForeName>Alexander</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Brock</LastName><ForeName>Guy</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Montefiori</LastName><ForeName>David C</ForeName><Initials>DC</Initials></Author><Author ValidYN="Y"><LastName>Vojdani</LastName><ForeName>Fakhrieh</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>McCormick</LastName><ForeName>Alison A</ForeName><Initials>AA</Initials></Author><Author ValidYN="Y"><LastName>O'Keefe</LastName><ForeName>Barry R</ForeName><Initials>BR</Initials></Author><Author ValidYN="Y"><LastName>Palmer</LastName><ForeName>Kenneth E</ForeName><Initials>KE</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>T32 ES011564</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI076169</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><Agency>Intramural NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>AI076169</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32-ES011564</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HHSN27201100016C</GrantID><Agency>PHS HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D052060">Research Support, N.I.H., Intramural</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2013</Year><Month>10</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Antimicrob Agents Chemother</MedlineTA><NlmUniqueID>0315061</NlmUniqueID><ISSNLinking>0066-4804</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015699">HIV Envelope Protein gp120</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D037121">Plant Lectins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C514793">gp120 protein, Human immunodeficiency virus 1</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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