Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19

In the early stages of drug discovery, researchers develop assays that are compatible with high throughput screening (HTS) and structure activity relationship (SAR) measurements. These assays are designed to evaluate the effectiveness of new and known molecular entities, typically targeting specific features within the virus. Drugs that inhibit virus replication by inhibiting a host gene or pathway are often missed because the goal is to identify active antiviral agents against known viral targets. Screening efforts should be sufficiently robust to identify all potential targets regardless of the antiviral mechanism to avoid misleading conclusions.

Automated summary

In the early stages of drug discovery, assays are developed to evaluate the effectiveness of new and known molecular entities, primarily targeting specific features within the virus. However, screening efforts often prioritize finding active antiviral drugs against known viral targets, overlooking drugs that inhibit virus replication by targeting host genes or pathways.