Discovery of sclareol and sclareolide as filovirus entry inhibitors

Abstract

Filoviruses cause severe hemorrhagic fever in humans. Ebola virus (EBOV) is the most contagious filovirus. Although compassionate treatments have been used during the latest Ebola outbreak, novel anti-EBOV agents are still urgently needed. In this study, sclareol and sclareolide, two natural products in Salvia sclarea, were identified as EBOV entry inhibitors with EC₅₀s of 2.4 μmol/L and 8.0 μmol/L, respectively, through blocking the viral fusion process. Moreover, both compounds exhibited inhibitory effects on all tested filoviruses’ entry, indicating their wide-spectrum activities against filoviruses. This study provides insights into the two natural products and their applications against filovirus infectious diseases.

Graphical Abstract

Keywords:

• Sclareol
• sclareolide
• Ebola
• filovirus
• entry inhibitor

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by grants from the National Natural Science Foundation of China (81202568, 81273561 and 81473256), the Drug Innovation Major Project (2015ZX09102-023 and 2018ZX09711001-003-002), the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-014), the Opening Foundation of the State Key Laboratory of Bioactive Substance and Function of Natural Medicines (GTZK201907), the Science and Technology Program of Beijing (Z151100000115008), and the Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150).