Abstract
Ebola virus (EBOV), one of the most infectious human viruses and a leading cause of viral hemorrhagic fever, imposes a potential public health threat with several recent outbreaks. Despite the difficulties associated with working with this pathogen in biosafety level-4 containment, a protective vaccine and antiviral therapeutic were recently approved. However, the high mortality rate of EBOV infection underscores the necessity to continuously identify novel antiviral strategies to help expand the scope of prophylaxis/therapeutic management against future outbreaks. This includes identifying antiviral agents that target EBOV entry, which could improve the management of EBOV infection. Herein, using EBOV glycoprotein (GP)-pseudotyped particles, we screened a panel of natural medicinal extracts, and identified the methanolic extract of Perilla frutescens (PFME) as a robust inhibitor of EBOV entry. We show that PFME dose-dependently impeded EBOV GP-mediated infection at non-cytotoxic concentrations, and exerted the most significant antiviral activity when both the extract and the pseudoparticles are concurrently present on the host cells. Specifically, we demonstrate that PFME could block viral attachment and neutralize the cell-free viral particles. Our results, therefore, identified PFME as a potent inhibitor of EBOV entry, which merits further evaluation for development as a therapeutic strategy against EBOV infection.
Highlights
Ebola virus (EBOV), the etiologic agent of Ebola virus disease (EVD), is an enveloped negative-sense single-stranded RNA virus, belonging to the Filoviridae family
Further western blot analysis confirmed the production of authentic EBOV pseudoparticles (EBOVpp), whereby in contrast to detecting the human immunodeficiency virus (HIV)-1 matrix protein p17 across the samples of pseudoparticles bearing vesicular stomatitis virus (VSV) glycoprotein G or EBOV GP, EBOV GP was only detected in the EBOVpp (Figure 1C)
Identifying antiviral agents that restrict EBOV entry into host cells and prevent establishment or limit propagation of its infection are advantageous as they could serve as therapeutic drugs, and for prophylaxis purposes which is key in reducing viral transmission and providing protection for high-risk healthcare workers [37]
Summary
Ebola virus (EBOV), the etiologic agent of Ebola virus disease (EVD), is an enveloped negative-sense single-stranded RNA virus, belonging to the Filoviridae family. This family of viruses includes the Marburg virus and is characterized by a thread-like, filamentous morphology [1]. Several recent localized outbreaks have occurred between 2018 and 2021, including the 2021 epidemics in the Democratic Republic of Congo [5] and Guinea [6]. The combination monoclonal antibody-based treatment Inmazeb (previously REGN-EB3), was approved by the U.S FDA in October
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