Screening Drugs for Broad-Spectrum, Host-Directed Antiviral Activity: Lessons from the Development of Probenecid for COVID-19
Ralph A. Tripp, David E. Martin
Abstract
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.
Topics & Concepts
Drug discoveryComputational biologyCoronavirus disease 2019 (COVID-19)Antiviral drugMechanism (biology)VirusDrug developmentBroad spectrumDrugViral replicationHost (biology)ProbenecidHost factorsBiologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)High-throughput screeningVirologyBioinformaticsMedicinePharmacologyChemistryGeneticsInfectious disease (medical specialty)EpistemologyPathologyPhilosophyCombinatorial chemistryDiseaseSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesInfluenza Virus Research Studies