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Front Pharmacol. 2018 Oct 23;9:1207. doi: 10.3389/fphar.2018.01207. eCollection 2018.
Investigating Different Mechanisms of Action in Combination Therapy for Influenza.
Melville K1, Rodriguez T2, Dobrovolny HM2.
Author information
Abstract
Combination therapy for influenza can have several benefits, from reducing the emergence of drug resistant virus strains to decreasing the cost of antivirals. However, there are currently only two classes of antivirals approved for use against influenza, limiting the possible combinations that can be considered for treatment. However, new antivirals are being developed that target different parts of the viral replication cycle, and their potential for use in combination therapy should be considered. The role of antiviral mechanism of action in the effectiveness of combination therapy has not yet been systematically investigated to determine whether certain antiviral mechanisms of action pair well in combination. Here, we use a mathematical model of influenza to model combination treatment with antivirals having different mechanisms of action to measure peak viral load, infection duration, and synergy of different drug combinations. We find that antivirals that lower the infection rate and antivirals that increase the duration of the eclipse phase perform poorly in combination with other antivirals.
KEYWORDS:
antiviral; combination therapy; influenza; mathematical modeling; mechanism of action
PMID: 30405419 PMCID: PMC6206389 DOI: 10.3389/fphar.2018.01207
Free full text
Investigating Different Mechanisms of Action in Combination Therapy for Influenza.
Melville K1, Rodriguez T2, Dobrovolny HM2.
Author information
Abstract
Combination therapy for influenza can have several benefits, from reducing the emergence of drug resistant virus strains to decreasing the cost of antivirals. However, there are currently only two classes of antivirals approved for use against influenza, limiting the possible combinations that can be considered for treatment. However, new antivirals are being developed that target different parts of the viral replication cycle, and their potential for use in combination therapy should be considered. The role of antiviral mechanism of action in the effectiveness of combination therapy has not yet been systematically investigated to determine whether certain antiviral mechanisms of action pair well in combination. Here, we use a mathematical model of influenza to model combination treatment with antivirals having different mechanisms of action to measure peak viral load, infection duration, and synergy of different drug combinations. We find that antivirals that lower the infection rate and antivirals that increase the duration of the eclipse phase perform poorly in combination with other antivirals.
KEYWORDS:
antiviral; combination therapy; influenza; mathematical modeling; mechanism of action
PMID: 30405419 PMCID: PMC6206389 DOI: 10.3389/fphar.2018.01207
Free full text