摘要：SummaryCurrently available SARS-CoV-2 therapeutics are targeted toward moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. Although vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replicationin vitroat a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways previously associated with poor SARS-CoV-2 disease outcomes. In addition, SNX-5422 interrupted expression of host factors demonstrated to be crucial for SARS-CoV-2 replication. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.Graphical abstractDisplay OmittedHighlights•SNX-5422 inhibits SARS-CoV-2 replicationin vitroat a high selectivity index•Transcriptomic profile of human airway epithelial cells treated with SNX-5422•SNX-5422 dampens proinflammatory pathways associated with poor COVID outcomes•SNX-5422 targets host factors crucial for SARS-CoV-2 replicationTherapeutics; Virology
