Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium

Hanlu Fan, Xiaohong Du, Jingyuan Zhang, Han Zheng, Xiaohui Lu, Qihui Wu, Haifeng Li, Han Wang, Yi Shi, George Gao, Zhuan Zhou, Dun Xian Tan, Xiangdong Li

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection. Herein, we demonstrated that the same dosages of SERMs which induced cholesterol accumulation also inhibited Ebola infection. SERMs reduced the cellular sphingosine and subsequently caused endolysosomal calcium accumulation, which in turn led to blocking the Ebola entry. Our study clarified the specific anti-Ebola mechanism of SERMs, even the cationic amphiphilic drugs (CADs), this mechanism led to the endolysosomal calcium as a critical target for development of anti-Ebola drugs.

Original languageEnglish (US)
Article number41226
JournalScientific reports
Volume7
DOIs
StatePublished - Jan 24 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium'. Together they form a unique fingerprint.

  • Cite this

    Fan, H., Du, X., Zhang, J., Zheng, H., Lu, X., Wu, Q., Li, H., Wang, H., Shi, Y., Gao, G., Zhou, Z., Tan, D. X., & Li, X. (2017). Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium. Scientific reports, 7, [41226]. https://doi.org/10.1038/srep41226