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Kevin P Anderson - One of the best experts on this subject based on the ideXlab platform.

  • Antiviral Activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus rna when used in combination with Antiviral nucleoside analogs
    Antiviral Research, 1995
    Co-Authors: Raana F Azad, Robert W Buckheit, Vickie L Browndriver, Kevin P Anderson
    Abstract:

    Abstract ISIS 2922 is a phosphorothioate oligonucleotide with potent Antiviral Activity against human cytomegalovirus (HCMV) in cell culture assays. The ability of ISIS 2922 to inhibit replication of HCMV when used in combination with other Antiviral agents approved for treatment of HCMV disease was investigated using a 96-well immunoassay. The Antiviral Activity of ISIS 2922 against HCMV was additive with that of ganciclovir (9-(1,3-dihydroxy-2-propoxymethylguanine); DHPG) or foscarnet (phosphonoformate). Compounds used clinically for the treatment of human immunodeficiency virus infection and likely to be co-administered with ISIS 2922 in the clinic were also evaluated for their ability to modulate the Antiviral Activity of ISIS 2922. 3′-Azido-3′-deoxythymidine (AZT) exhibited no Antiviral Activity against HCMV in the 96-well immunoassay, and did not significantly alter the Antiviral Activity of ISIS 2922. 2′-3′-Dideoxycytidine (ddC) was able to inhibit replication of HCMV at high doses, and this Activity was additive with that of ISIS 2922. ISIS 2922 inhibited HIV replication in acute infection assays at relatively high concentrations as previously reported for non-complementary phosphorothioate oligonucleotides. When ISIS 2922 was used in combination with AZT in this assay, interactions were additive at most concentrations, although significant and reproducible synergy was observed at some concentration combinations.

  • Antiviral Activity of a phosphorothioate oligonucleotide complementary to rna of the human cytomegalovirus major immediate early region
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Raana F Azad, V B Driver, K Tanaka, R M Crooke, Kevin P Anderson
    Abstract:

    Phosphorothioate oligonucleotides complementary to mRNA of the human cytomegalovirus (HCMV) DNA polymerase gene or to RNA transcripts of the major immediate-early regions 1 and 2 (IE1 and IE2) of HCMV were evaluated for Antiviral Activity in a 96-well immunoassay with primary human dermal fibroblasts as host cells. Oligonucleotides complementary to RNA of the IE2 region exhibited the most potent Antiviral Activity. One of these oligonucleotides, ISIS 2922, was at least 30-fold more potent than the nucleoside analog, ganciclovir, with a 50% effective concentration of 0.37 microM in the 96-well immunoassay. In an infectious virus yield reduction assay, ISIS 2922 and ganciclovir reduced production of infectious virus by 2 log units at concentrations of 2.2 and 36 microM, respectively. A control oligonucleotide showed no inhibition of virus production at concentrations as high as 3 microM. ISIS 2922 reduced IE protein synthesis in HCMV-infected cells in a dose-dependent manner which correlated with Antiviral Activity. The Antiviral Activity of ISIS 2922 was not due to oligonucleotide-induced cytotoxicity since effects on cell viability or proliferation were observed only at concentrations well in excess of effective Antiviral concentrations. The specificity and potency of ISIS 2922 suggest that it may be useful for the treatment of cytomegalovirus disease in humans. Images

Ling Peng - One of the best experts on this subject based on the ideXlab platform.

Alberto S Cerezo - One of the best experts on this subject based on the ideXlab platform.

  • the structure of the agaran sulfate from acanthophora spicifera rhodomelaceae ceramiales and its Antiviral Activity relation between structure and Antiviral Activity in agarans
    Carbohydrate Research, 2004
    Co-Authors: Maria Eugenia R Duarte, Jean P Cauduro, Diego Gabriel Noseda, Miguel D Noseda, Alan G Goncalves, Carlos A Pujol, Elsa B Damonte, Alberto S Cerezo
    Abstract:

    Abstract The sulfated agaran isolated by water extraction from the red seaweed, Acanthophora spicifera (Rhodomelaceae, Ceramiales), is made up of A-units highly substituted with sulfate groups on C-2 (28–30%), sulfates on C-2 and 4,6-O-(1′-carboxyethylidene) groups (9–15%), and only the C-2 sulfate groups (5–8%) with small amounts of C-6 sulfate, 6-O-methyl, and nonsubstituted residues. B-units are formed mainly by 3,6-anhydro-α- l -galactose (15–16%) and its precursor, α- l -galactose 6-sulfate (10–17%), together with lesser amounts of 3,6-anhydro-α- l -galactose 2-sulfate, α- l -galactose 2,6-disulfate, α- l -galactose 2,3,6-tri-sulfate, α- l -galactose 2,6-disulfate 3-xylose, 2-O-methyl-α- l -galactose, and unsubstituted α- l -galactose. Small, but significant quantities of β- d -xylose were found in all the fractions, together with small amounts to traces of d -glucose. Some of the fractions have high Antiviral Activity. Attempts to correlate structure and Antiviral Activity in agarans are presented.

  • the structure of the agaran sulfate from acanthophora spicifera rhodomelaceae ceramiales and its Antiviral Activity relation between structure and Antiviral Activity in agarans
    Carbohydrate Research, 2004
    Co-Authors: Maria Eugenia R Duarte, Jean P Cauduro, Diego Gabriel Noseda, Miguel D Noseda, Alan G Goncalves, Carlos A Pujol, Elsa B Damonte, Alberto S Cerezo
    Abstract:

    The sulfated agaran isolated by water extraction from the red seaweed, Acanthophora spicifera (Rhodomelaceae, Ceramiales), is made up of A-units highly substituted with sulfate groups on C-2 (28-30%), sulfates on C-2 and 4,6-O-(1'-carboxyethylidene) groups (9-15%), and only the C-2 sulfate groups (5-8%) with small amounts of C-6 sulfate, 6-O-methyl, and nonsubstituted residues. B-units are formed mainly by 3,6-anhydro-alpha-L-galactose (15-16%) and its precursor, alpha-L-galactose 6-sulfate (10-17%), together with lesser amounts of 3,6-anhydro-alpha-L-galactose 2-sulfate, alpha-L-galactose 2,6-disulfate, alpha-L-galactose 2,3,6-tri-sulfate, alpha-L-galactose 2,6-disulfate 3-xylose, 2-O-methyl-alpha-L-galactose, and unsubstituted alpha-L-galactose. Small, but significant quantities of beta-D-xylose were found in all the fractions, together with small amounts to traces of D-glucose. Some of the fractions have high Antiviral Activity. Attempts to correlate structure and Antiviral Activity in agarans are presented.

Raana F Azad - One of the best experts on this subject based on the ideXlab platform.

  • Antiviral Activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus rna when used in combination with Antiviral nucleoside analogs
    Antiviral Research, 1995
    Co-Authors: Raana F Azad, Robert W Buckheit, Vickie L Browndriver, Kevin P Anderson
    Abstract:

    Abstract ISIS 2922 is a phosphorothioate oligonucleotide with potent Antiviral Activity against human cytomegalovirus (HCMV) in cell culture assays. The ability of ISIS 2922 to inhibit replication of HCMV when used in combination with other Antiviral agents approved for treatment of HCMV disease was investigated using a 96-well immunoassay. The Antiviral Activity of ISIS 2922 against HCMV was additive with that of ganciclovir (9-(1,3-dihydroxy-2-propoxymethylguanine); DHPG) or foscarnet (phosphonoformate). Compounds used clinically for the treatment of human immunodeficiency virus infection and likely to be co-administered with ISIS 2922 in the clinic were also evaluated for their ability to modulate the Antiviral Activity of ISIS 2922. 3′-Azido-3′-deoxythymidine (AZT) exhibited no Antiviral Activity against HCMV in the 96-well immunoassay, and did not significantly alter the Antiviral Activity of ISIS 2922. 2′-3′-Dideoxycytidine (ddC) was able to inhibit replication of HCMV at high doses, and this Activity was additive with that of ISIS 2922. ISIS 2922 inhibited HIV replication in acute infection assays at relatively high concentrations as previously reported for non-complementary phosphorothioate oligonucleotides. When ISIS 2922 was used in combination with AZT in this assay, interactions were additive at most concentrations, although significant and reproducible synergy was observed at some concentration combinations.

  • Antiviral Activity of a phosphorothioate oligonucleotide complementary to rna of the human cytomegalovirus major immediate early region
    Antimicrobial Agents and Chemotherapy, 1993
    Co-Authors: Raana F Azad, V B Driver, K Tanaka, R M Crooke, Kevin P Anderson
    Abstract:

    Phosphorothioate oligonucleotides complementary to mRNA of the human cytomegalovirus (HCMV) DNA polymerase gene or to RNA transcripts of the major immediate-early regions 1 and 2 (IE1 and IE2) of HCMV were evaluated for Antiviral Activity in a 96-well immunoassay with primary human dermal fibroblasts as host cells. Oligonucleotides complementary to RNA of the IE2 region exhibited the most potent Antiviral Activity. One of these oligonucleotides, ISIS 2922, was at least 30-fold more potent than the nucleoside analog, ganciclovir, with a 50% effective concentration of 0.37 microM in the 96-well immunoassay. In an infectious virus yield reduction assay, ISIS 2922 and ganciclovir reduced production of infectious virus by 2 log units at concentrations of 2.2 and 36 microM, respectively. A control oligonucleotide showed no inhibition of virus production at concentrations as high as 3 microM. ISIS 2922 reduced IE protein synthesis in HCMV-infected cells in a dose-dependent manner which correlated with Antiviral Activity. The Antiviral Activity of ISIS 2922 was not due to oligonucleotide-induced cytotoxicity since effects on cell viability or proliferation were observed only at concentrations well in excess of effective Antiviral concentrations. The specificity and potency of ISIS 2922 suggest that it may be useful for the treatment of cytomegalovirus disease in humans. Images

Yi Xia - One of the best experts on this subject based on the ideXlab platform.