Ebola Entry Inhibitors Discovered from Maesa perlarius.

Nga Yi Tsang,Elizabeth Varhegyi,Lijun Rong,Wan-Fei Li,Hong-Jie Zhang

doi:10.3390/ijms23052620

Nga Yi Tsang, Elizabeth Varhegyi + Show 3 more

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https://doi.org/10.3390/ijms23052620

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Abstract

Ebola virus disease (EVD), a disease caused by infection with Ebola virus (EBOV), is characterized by hemorrhagic fever and a high case fatality rate. With limited options for the treatment of EVD, anti-Ebola viral therapeutics need to be urgently developed. In this study, over 500 extracts of medicinal plants collected in the Lingnan region were tested against infection with Ebola-virus-pseudotyped particles (EBOVpp), leading to the discovery of Maesa perlarius as an anti-EBOV plant lead. The methanol extract (MPBE) of the stems of this plant showed an inhibitory effect against EBOVpp, with an IC50 value of 0.52 µg/mL, which was confirmed by testing the extract against infectious EBOV in a biosafety level 4 laboratory. The bioassay-guided fractionation of MPBE resulted in three proanthocyanidins (procyanidin B2 (1), procyanidin C1 (2), and epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin-(4β→8)-epicatechin (3)), along with two flavan-3-ols ((+)-catechin (4) and (−)-epicatechin (5)). The IC50 values of the compounds against pseudovirion-bearing EBOV-GP ranged from 0.83 to 36.0 µM, with 1 as the most potent inhibitor. The anti-EBOV activities of five synthetic derivatives together with six commercially available analogues, including EGCG ((−)-epigallocatechin-3-O-gallate (8)), were further investigated. Molecular docking analysis and binding affinity measurement suggested the EBOV glycoprotein could be a potential molecular target for 1 and its related compounds.

Highlights

Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), a disease associated with hemorrhagic fever and high case fatality rates [1–3]
We report on structural isolation, isolation, determination, and modification and evaluate the anti-EBOV activity of the determination, and modification identified polyphenol compounds. and evaluate the anti-EBOV activity of the identified polyphenol compounds
The screening of Lingnan plant extracts led to the identification

Summary

Introduction

Ebola virus (EBOV) is the causative agent of Ebola virus disease (EVD), a disease associated with hemorrhagic fever and high case fatality rates [1–3]. With limited therapeutic options and a current outbreak of Ebola virus disease in Africa, there is an urgent need to develop novel anti-EBOV agents [4]. The study of anti-EBOV agents is largely hampered by the requirement of biosafety level 4 (BSL-4) containments. To search for inhibitors of Ebola virus, we used a cell-based assay with replication-incompetent pseudotyped viral particles that express a specific viral glycoprotein on the surface and can be performed in a BSL-2 containment [5]. The development of the “one-stone-two-birds” protocol was first reported in 2011 [6]. This approach has been subsequently applied in our plant drug discovery program and assisted in our successful discovery of a number of antiviral lead compounds [5,7–10]

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