Medicinal plants as source of antiviral substances against respiratory syncytial virus

Abstract

This thesis aimed to investigate Rwandan medicinal plants as a possible source of candidate antiviral compounds against respiratory syncytial virus (RSV), a pathogen causing severe respiratory infections with limited treatment options. Using an ethnopharmacological approach, the study sought to document plants used by traditional healers (THs), evaluate their anti-RSV activity, and isolate and characterize bioactive compounds. An ethnomedicinal survey involving 40 THs recorded 48 plant species used to treat respiratory conditions. Sequential extraction of plant materials yielded 203 extracts, which were assessed for RSV inhibition and cytotoxicity in HEp-2 cells. The selected bioactive extracts were subjected to chromatographic separation, and compounds were structurally elucidated by spectroscopic and mass spectrometric analyses. Antiviral activity was further evaluated through virus yield reduction and resistance studies. Several extracts showed substantial anti-RSV activity (EC50: 1.6-39.5 µg/mL). The methanolic extract of Senecio maranguensis targeted the RSV fusion (F) protein, with resistance linked to a T335M mutation. Dicaffeoylquinic acid isomers, isolated from Conyza sumatrensis (S.F. Blake) Pruski & G. Sancho, exhibited potent activity (EC50 < 1 µM; SI > 100) and reduced viral titers by up to 3 log10 PFU. Resistance selection identified mutations in the RSV F protein, including K394R and I530M, further supporting a mechanism of action involving inhibition of viral fusion. Additionally, phytochemical investigation of Croton kilwae yielded new and known crotofolane diterpenoids and other compounds, some of which showed moderate anti-RSV activity. Structural features, including isomerism, influenced antiviral potency and resistance. In conclusion, this thesis highlights medicinal plants as a valuable source of anti-RSV compounds. Dicaffeoylquinic acid derivatives targeting the RSV F protein emerge as promising leads for antiviral drug development, supporting the potential of ethnopharmacology-guided discovery.