25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor.
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ABSTRACT:
SUBMITTER: Zu S
PROVIDER: S-EPMC7431750 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor.
Zu Shulong S Deng Yong-Qiang YQ Zhou Chao C Li Jie J Li Lili L Chen Qi Q Li Xiao-Feng XF Zhao Hui H Gold Sarah S He Jun J Li Xiang X Zhang Changqing C Yang Heng H Cheng Genhong G Qin Cheng-Feng CF
Cell research 20200818 11
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Project description:Here we identify halofuginone, a Prolyl-tRNA Synthetase (PRS) inhibitors as a potent inhibitors of SARS-CoV-2 cellular entry and viral replication. To infect the host cell, the SARS-CoV-2 spike protein interacts with cell surface heparan sulfate (HS) and angiotensin-converting enzyme 2 (ACE2) through its Receptor Binding Domain. Removal of cell surface HS or blockade of HS biosynthesis represents a promising clinical target for treatment of SARS-CoV-2. In vitro studies confirm that halofuginone and PRS inhibitors prevent HS biosynthesis and thereby HS cell surface presentation and Spike protein binding. Halofuginone also suppresses authentic SARS-CoV-2 infection by inhibiting PRS activity, which decreases the translation efficiency of proline-rich HS biosynthetic enzymes and essential SARS-CoV-2 proteins after infection (data not provided here). Thus, halofuginone inhibits SARS-CoV-2 at both attachment and post-entry steps and blocks SARS-CoV-2 infection of human lung airway epithelial cells at low nanomolar concentrations. These findings support the use of halofuginone, an orally bioavailable anti-fibrotic and anti-inflammatory compound with encouraging clinical phase 1 safety data, as an antiviral drug to prevent SARS-CoV-2 infection.
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