Plants extracts from Cameroon pharmacopeia strongly inhibit the Chikungunya virus infection by targeting entry and replication steps

Abstract

Ethnopharmacological relevance: Cameroon is one of the sub-Saharan African countries affected by Chikungunya virus (CHIKV). With the absence of approved treatment, this disease represents globally a major public health concern. Several plants are traditionally used in Cameroon for the treatment of virus induced fever and arthralgia. But to date there is no study that validate the efficacy of these plants for the treatment of Chikungunya virus infection.

Aim of the study: This study aims to explore the inhition effect, mechanism of action of plant extracts against Chikungunya virus.

Material and methods: An ethnobotanical survey conducted in some regions of Cameroon, led to the identification of nine medicinal plants used in traditional medicine for the healing of fever-related diseases and arthritis. Crude hydro-ethanolic extracts of each plant were prepared by maceration and their effects against CHIKV infection were investigated. CHIKV S27 strain was used to infection in Vero cell line. The antiviral activities were determined by plaque assay and/or RT-PCR targeting E1 envelope gene of CHIKV. Dose-response studies of the active plants were also determined by flow cytometry and Western blot.

Results: Four extracts, Entada africana Guill et Pers. (E4), Entandrophragma cylindricum Sprague (EI), Khaya grandifoliola C. D.C. Sapindales (E2) and Macaranga hurifolia Beille (E6) showed antiviral activity with the half-maximal inhibitory concentration of 8.29; 8.14; 12.81 and 26.89 μg/mL respectively. All extracts were nontoxic up to the concentration of 100 μg/μL. Entandrophragma cylindricum Sprague (EI), Khaya grandifoliola C. D.C. Sapindales (E2), and Entada africana Guill et Pers. (E4) showed strong inhibition on the entry step of viral infection. At the same time, only Entandrophragma cylindricum Sprague (EI) inhibited the viral titer significantly in replication and intercellular assembly steps. Four plant extracts namely Entandrophragma cylindricum Sprague (EI), Macaranga hurifolia Beille (E6), Phragmentera capitata (Sprengel) Balle (E12), and Detarium microcarpum (E13) were effective against egression step.

Conclusions: Together, the results of this study showed anti-chikungunya activities of Entandrophragma cylindricum Sprague (EI) and Macaranga hurifolia Beille (E6), with therapeutics perspectives and can be promising sources of the development of anti-CHIKV molecule in future.

Keywords: Antiviral activities; Chikungunya virus; Entandrophragma cylindricum Sprague; Entry step; Plants extract; Replication.