Learning from the In Vitro Biological Activity Data of Current Antiviral Medicines for the Successful Development of New Antiviral Drug Candidates

Abstract

Background: Although evaluating in vitro biological activity is an important part of the drug discovery process, few publications discuss the ideal inhibitory activity in these tests. Objective: To analyze the in vitro biological activity data from antiviral drugs to establish parameters that could increase success in developing new antiviral drug candidates. Methods: Information from in vitro tests for each antiviral medicine was obtained from the Thomson Reuters Integrity platform for antiviral drugs approved by FDA between 1963 and 2020 (35 years). The inhibitory activity data was collected from three references using the same determination method, and the values were reported as means. Results: 82 antiviral drugs were found to treat 11 different viruses. Most of these drugs were developed to treat HIV infections (33 of 82), followed by anti-HCV medicines (20 of 82). The anti-HIV phenotypic activities of most HIV-approved drugs had an IC50 < 50 nM; for the anti-HCV it was verified as IC50 < 0.2 μM. Combining the data for all drugs analyzed, the antiviral phenotypic activity in most cases exhibited an IC50 < 0.2 μM. Conclusions: The limited availability of antiviral drugs and in vitro activity data imposed limitations on this study. However, it could be inferred that an antiviral drug candidate would have more success in drug development when the IC50 was in the range of low micromolar. Ultimately, in vitro activity must be considered in combination with other factors in drug development processes.