A SARS-CoV-2 antiviral therapy score card

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The COVID-19 pandemic has unleashed an unprecedented effort to identify efficacious treatments for persons infected with SARS-CoV-2. As of September 2020, more than 750 completed, ongoing, or planned clinical trials of drugs intended to inhibit SARS-CoV-2 replication have been registered on the ClinicalTrials.gov or WHO International Clinical Trials Platform websites. Most of the treatments studied in these trials are repurposed licensed or investigational drugs targeting viral proteins or cellular pathways required for virus replication. The use of repurposed compounds is understandable because with the exception of monoclonal antibodies, it will be several months before novel SARS-CoV-2-specific drugs will be available for human testing. This editorial describes those compounds that I believe should be prioritized for clinical testing: i) viral RNA polymerase inhibitors including GS-441524, its prodrug remdesivir, and EIDD-2801; ii) entry inhibitors including monoclonal antibodies, ACE2 molecular decoys, and peptide fusion inhibitors; iii) parenteral and inhalational preparations of interferon β and λ; and iv) inhibitors of host transmembrane protease serine 2 (TMPRSS2), endosomal trafficking, and pyrimidine synthesis. As SARS-CoV-2 is pandemic and as its most severe consequences result from a dysregulated immunological response to infection, the ideal therapies should be inexpensive and should be able to be administered to non-hospitalized persons at the time of their initial diagnosis.