tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Haoran Peng[SUP] 1 [/SUP], Hailin Tang[SUP] 1 [/SUP], Yangang Liu[SUP] 1 [/SUP], Xu Zheng[SUP] 1 [/SUP], Bin Liu[SUP] 1 [/SUP], Liangliang Jiang[SUP] 1 [/SUP], Wanda Tang[SUP] 1 [/SUP], Yanhua He[SUP] 1 [/SUP], Yan Liu[SUP] 1 [/SUP], Hao Ren[SUP] 1 [/SUP], Ping Zhao[SUP] 1 [/SUP], Zhongtian Qi[SUP] 1 [/SUP], Cuiling Ding[SUP] 1 [/SUP]
Affiliations
Abstract
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.
. 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[SUP] 1 [/SUP], Haoran Peng[SUP] 1 [/SUP], Hailin Tang[SUP] 1 [/SUP], Yangang Liu[SUP] 1 [/SUP], Xu Zheng[SUP] 1 [/SUP], Bin Liu[SUP] 1 [/SUP], Liangliang Jiang[SUP] 1 [/SUP], Wanda Tang[SUP] 1 [/SUP], Yanhua He[SUP] 1 [/SUP], Yan Liu[SUP] 1 [/SUP], Hao Ren[SUP] 1 [/SUP], Ping Zhao[SUP] 1 [/SUP], Zhongtian Qi[SUP] 1 [/SUP], Cuiling Ding[SUP] 1 [/SUP]
Affiliations
- PMID: 35733297
- DOI: 10.1002/jmv.27951
Abstract
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.