Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry

Ke Tang; Xiaoyu Zhang; Ying Guo

doi:10.1016/j.apsb.2020.02.014

Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry

Acta Pharm Sin B. 2020 May;10(5):789-798. doi: 10.1016/j.apsb.2020.02.014. Epub 2020 Mar 5.

Authors

Ke Tang^{1

2}, Xiaoyu Zhang^{1

2}, Ying Guo^{1

2}

Affiliations

¹ State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
² Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

Abstract

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC₅₀ of 6.9-10.0 μmol/L using an HIV based pseudovirus platform. Capsaicin inhibits the entry of five LASV strains but not against the Old World arenavirus lymphocytic choriomeningitis virus (LCMV), showing a preferential activity against LASV. Capsaicin inhibits LASV entry by blocking the pH dependent viral fusion through affecting the stable signal peptide (SSP)-GP2 transmembrane (GP2_TM) region of the LASV surface glycoprotein. Mutational study revealed the key residues Ala25, Val431, Phe434 and Val435 in SSP-GP2_TM region in capsaicin's antiviral effect. This study for the first time reveals a direct acting antiviral effect of capsaicin against the hemorrhagic fever causing LASV, providing detailed interaction hot spots in the unique SSP-GP2_TM interface of LASV glycoprotein that is crucial in fusion inhibition, and offering a new strategy in discovering and developing antivirals from natural products that are safe for human use.

Keywords: Capsaicin; Dietary supplement; Fusion inhibitor; Hemorrhagic fever; Lassa virus; Natural product antivirals; SSP-GP2TM region; Viral entry.