A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals

Laura Riva; Shuofeng Yuan; Xin Yin; Laura Martin-Sancho; Naoko Matsunaga; Sebastian Burgstaller-Muehlbacher; Lars Pache; Paul P. De Jesus; Mitchell V. Hull; Max Chang; Jasper Fuk-Woo Chan; Jianli Cao; Vincent Kwok-Man Poon; Kristina Herbert; Tu-Trinh Nguyen; Yuan Pu; Courtney Nguyen; Andrey Rubanov; Luis Martinez-Sobrido; Wen-Chun Liu; Lisa Miorin; Kris M. White; Jeffrey R. Johnson; Christopher Benner; Ren Sun; Peter G. Schultz; Andrew Su; Adolfo Garcia-Sastre; Arnab K. Chatterjee; Kwok-Yung Yuen; Sumit K. Chanda

Here, we describe a high-throughput analysis of the ReFRAME library to identify inhibitors of SARS-CoV-2 replication in mammalian cells, and identified several targets and mechanistic classes that were highly enriched, including aldose reductase inhibitors, retinoic acid receptor antagonists, benzodiazepine receptor agonists, regulators of cholesterol homeostasis and antimalarial compounds. Validation studies further confirmed 30 known drugs to inhibit viral replication, including four molecules previously approved by the FDA (clofazimine, acitretin, tretinoin, and astemizole) or registered outside the US (tamibarotene). Dose response studies have thus far author/funder. All rights reserved. No reuse allowed without permission.