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Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells
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| Zeitschriftentitel: | Antimicrobial Agents and Chemotherapy |
|---|---|
| Personen und Körperschaften: | , , , |
| In: | Antimicrobial Agents and Chemotherapy, 48, 2004, 12, S. 4855-4863 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. |
|---|---|
| author |
Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. |
| spellingShingle |
Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. Antimicrobial Agents and Chemotherapy Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells Infectious Diseases Pharmacology (medical) Pharmacology |
| author_sort |
govorkova, elena a. |
| spelling |
Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.48.12.4855-4863.2004 <jats:title>ABSTRACT</jats:title> <jats:p>There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine against infection of MDCK cells with H1N1 and H3N2 subtypes of influenza A virus and characterized their mode of interaction. When reduction of extracellular virus was analyzed by individual regression models and three-dimensional representations of the data, all three combinations showed additive and synergistic effects with no cytotoxicity. Maximum synergy against A/New Caledonia/20/99 (H1N1) virus infection was observed with <2.5 μM rimantadine paired with low concentrations of NA inhibitors. All combinations reduced the extracellular yield of A/Panama/2007/99 (H3N2) influenza virus synergistically. However, our findings were different for the cell-associated virus yield. At some drug concentrations, the yield of cell-associated virus was inhibited antagonistically. Therefore, the method of analysis can be a crucial factor in evaluating the interactions of drugs with different mechanisms. We hypothesize that assays based on cell-associated virus yield may underestimate the efficacies of drug combinations that include an NA inhibitor. Taken together, our results suggest that regimens that combine NA inhibitors and rimantadine exert synergistic anti-influenza effects in vitro. These findings provide baseline information for therapeutic testing of the drug combinations in vivo.</jats:p> Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells Antimicrobial Agents and Chemotherapy |
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American Society for Microbiology, 2004 |
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| title |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_unstemmed |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_full |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_fullStr |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_full_unstemmed |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_short |
Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_sort |
neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in mdck cells |
| topic |
Infectious Diseases Pharmacology (medical) Pharmacology |
| url |
http://dx.doi.org/10.1128/aac.48.12.4855-4863.2004 |
| publishDate |
2004 |
| physical |
4855-4863 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine against infection of MDCK cells with H1N1 and H3N2 subtypes of influenza A virus and characterized their mode of interaction. When reduction of extracellular virus was analyzed by individual regression models and three-dimensional representations of the data, all three combinations showed additive and synergistic effects with no cytotoxicity. Maximum synergy against A/New Caledonia/20/99 (H1N1) virus infection was observed with <2.5 μM rimantadine paired with low concentrations of NA inhibitors. All combinations reduced the extracellular yield of A/Panama/2007/99 (H3N2) influenza virus synergistically. However, our findings were different for the cell-associated virus yield. At some drug concentrations, the yield of cell-associated virus was inhibited antagonistically. Therefore, the method of analysis can be a crucial factor in evaluating the interactions of drugs with different mechanisms. We hypothesize that assays based on cell-associated virus yield may underestimate the efficacies of drug combinations that include an NA inhibitor. Taken together, our results suggest that regimens that combine NA inhibitors and rimantadine exert synergistic anti-influenza effects in vitro. These findings provide baseline information for therapeutic testing of the drug combinations in vivo.</jats:p> |
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| author | Govorkova, Elena A., Fang, Hong-Bin, Tan, Ming, Webster, Robert G. |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p>There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine against infection of MDCK cells with H1N1 and H3N2 subtypes of influenza A virus and characterized their mode of interaction. When reduction of extracellular virus was analyzed by individual regression models and three-dimensional representations of the data, all three combinations showed additive and synergistic effects with no cytotoxicity. Maximum synergy against A/New Caledonia/20/99 (H1N1) virus infection was observed with <2.5 μM rimantadine paired with low concentrations of NA inhibitors. All combinations reduced the extracellular yield of A/Panama/2007/99 (H3N2) influenza virus synergistically. However, our findings were different for the cell-associated virus yield. At some drug concentrations, the yield of cell-associated virus was inhibited antagonistically. Therefore, the method of analysis can be a crucial factor in evaluating the interactions of drugs with different mechanisms. We hypothesize that assays based on cell-associated virus yield may underestimate the efficacies of drug combinations that include an NA inhibitor. Taken together, our results suggest that regimens that combine NA inhibitors and rimantadine exert synergistic anti-influenza effects in vitro. These findings provide baseline information for therapeutic testing of the drug combinations in vivo.</jats:p> |
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| imprint_str_mv | American Society for Microbiology, 2004 |
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| spelling | Govorkova, Elena A. Fang, Hong-Bin Tan, Ming Webster, Robert G. 0066-4804 1098-6596 American Society for Microbiology Infectious Diseases Pharmacology (medical) Pharmacology http://dx.doi.org/10.1128/aac.48.12.4855-4863.2004 <jats:title>ABSTRACT</jats:title> <jats:p>There is insufficient information about combination therapy with approved anti-influenza agents. We tested combinations that paired a neuraminidase (NA) inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine against infection of MDCK cells with H1N1 and H3N2 subtypes of influenza A virus and characterized their mode of interaction. When reduction of extracellular virus was analyzed by individual regression models and three-dimensional representations of the data, all three combinations showed additive and synergistic effects with no cytotoxicity. Maximum synergy against A/New Caledonia/20/99 (H1N1) virus infection was observed with <2.5 μM rimantadine paired with low concentrations of NA inhibitors. All combinations reduced the extracellular yield of A/Panama/2007/99 (H3N2) influenza virus synergistically. However, our findings were different for the cell-associated virus yield. At some drug concentrations, the yield of cell-associated virus was inhibited antagonistically. Therefore, the method of analysis can be a crucial factor in evaluating the interactions of drugs with different mechanisms. We hypothesize that assays based on cell-associated virus yield may underestimate the efficacies of drug combinations that include an NA inhibitor. Taken together, our results suggest that regimens that combine NA inhibitors and rimantadine exert synergistic anti-influenza effects in vitro. These findings provide baseline information for therapeutic testing of the drug combinations in vivo.</jats:p> Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells Antimicrobial Agents and Chemotherapy |
| spellingShingle | Govorkova, Elena A., Fang, Hong-Bin, Tan, Ming, Webster, Robert G., Antimicrobial Agents and Chemotherapy, Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells, Infectious Diseases, Pharmacology (medical), Pharmacology |
| title | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_full | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_fullStr | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_full_unstemmed | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_short | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| title_sort | neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in mdck cells |
| title_unstemmed | Neuraminidase Inhibitor-Rimantadine Combinations Exert Additive and Synergistic Anti-Influenza Virus Effects in MDCK Cells |
| topic | Infectious Diseases, Pharmacology (medical), Pharmacology |
| url | http://dx.doi.org/10.1128/aac.48.12.4855-4863.2004 |