The determination of effective antiviral doses using a computer program for sigmoid dose-response curves

Area of Science:

• Virology
• Computational Biology
• Pharmacology

Background:

• Antiviral drug efficacy is often quantified by the effective dose (ED50), representing the dose required to inhibit viral activity by 50%.
• Accurate determination of ED50 is crucial for drug development and understanding antiviral resistance.
• Traditional methods like probit analysis have limitations in statistical parameter generation and goodness-of-fit evaluation.

Purpose of the Study:

• To develop and validate a computer program for constructing best-fit sigmoid dose-response curves.
• To determine the effective antiviral dose (ED50) of 9-beta-D-arabinofuranosyladenine against herpes simplex virus type 1 (HSV-1).
• To compare the ED50 values obtained from the new program with those from probit analysis.

Main Methods:

• Development of a computer program to generate sigmoid dose-response curves.
• Application of the program to analyze antiviral activity of 9-beta-D-arabinofuranosyladenine against four HSV-1 strains.
• Comparison of ED50 values derived from sigmoid curve fitting and probit analysis.
• Statistical evaluation of ED50 differences between resistant and sensitive strains and goodness-of-fit.

Main Results:

• The computer program successfully constructed best-fit sigmoid dose-response curves.
• ED50 values were determined for 9-beta-D-arabinofuranosyladenine against HSV-1 strains.
• Statistical parameters from the sigmoid fit program allowed for evaluation of differences between resistant and sensitive strains.
• The study demonstrated that experimental variables like multiplicity of infection significantly impact apparent ED50 values.

Conclusions:

• The developed computer program provides a robust method for determining antiviral ED50 values.
• This analytical approach facilitates statistical comparison of antiviral activities and aids in identifying drug resistance.
• The program is versatile, applicable to both plaque and yield reduction assays for comprehensive antiviral data analysis.