J Med Virol

. 2022 Jun 22.
doi: 10.1002/jmv.27951. Online ahead of print.
Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor

Gen Miao 1 , Haoran Peng 1 , Hailin Tang 1 , Yangang Liu 1 , Xu Zheng 1 , Bin Liu 1 , Liangliang Jiang 1 , Wanda Tang 1 , Yanhua He 1 , Yan Liu 1 , Hao Ren 1 , Ping Zhao 1 , Zhongtian Qi 1 , Cuiling Ding 1



Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh member of the coronavirus family that can infect humans. Recently, more contagious and pathogenic variants of SARS-CoV-2 have been continuously emerging. Clinical candidates with high efficacy and ready availability are still in urgent need. To identify potent anti-SARS-CoV-2 repurposing drugs, we evaluated the antiviral efficacy of 18 selective estrogen receptor modulators (SERMs) against SARS-CoV-2 infection. Six SERMs exhibited excellent anti-SARS-CoV-2 effects in Vero E6 cells and three human cell lines. Clomifene citrate, tamoxifen, toremifene citrate, and bazedoxifene acetate reduced the weight loss of hamsters challenged with SARS-CoV-2, and reduced hamster pulmonary viral load and IL-6 expression when assayed at 4 days post-infection. In particular, bazedoxifene acetate was identified to act on the penetration stage of the post-attachment step via altering cholesterol distribution and endosome acidification. And, bazedoxifene acetate inhibited pseudoviruses infection of original SARS-CoV-2, Delta variant, Omicron variant and SARS-CoV. These results offer critical information supporting bazedoxifene acetate as a promising agent against coronaviruses. This article is protected by copyright. All rights reserved.

Keywords: Severe acute respiratory syndrome coronavirus 2; bazedoxifene acetate; cholesterol distribution; endosome acidification; selective estrogen receptor modulator.