Activity of Geranium macrorrhizum extracts, essential oils and their main components against three relevant flagellated protozoa

Marcos-Herraiz, S.; Irisarri-Gutierrez, M. J.; Carrion, J.; Azami Conesa, I.; Suarez Lombao, R.; Navarro-Rocha, J.; Quilez, J. F.; Fernandez Barrero, A.; Ochoa, E.; Gonzalez Coloma, A.; Gomez Munoz, M. T.; Bailen, M.

doi:10.1101/2025.10.03.680318

bioRxiv · 10.1101/2025.10.03.680318

Activity of Geranium macrorrhizum extracts, essential oils and their main components against three relevant flagellated protozoa

Marcos-Herraiz, S.·Irisarri-Gutierrez, M. J.·Carrion, J.·Azami Conesa, I.·Suarez Lombao, R.·Navarro-Rocha, J.·Quilez, J. F.·Fernandez Barrero, A.·Ochoa, E.·Gonzalez Coloma, A.·Gomez Munoz, M. T.·Bailen, M.

View original source ↗Export metadata ↓

Abstract

Plant-derived natural products are structurally diverse secondary metabolites that play essential ecological roles and have long been recognized for their therapeutic potential. Geranium macrorrhizum is known to produce bioactive extracts and essential oils rich in monoterpenoids and sesquiterpenes. While various Geranium species have demonstrated antiprotozoal activity, the potential of G. macrorrhizum against protozoan parasites remains unexplored. Given the increasing resistance of protozoan pathogens to conventional treatments, there is a pressing need to identify alternative therapeutic agents from natural sources. Plant material was grown in greenhouse and aeroponic systems. Extracts were obtained via hydrodistillation and Soxhlet, and analyzed by GC-MS. In vitro assays were performed to evaluate antiparasitic activity and cytotoxicity. Morphological changes induced by germacrone were analyzed using light microscopy. The study evaluated the antiparasitic potential of essential oils, extracts, and compounds from Geranium macrorrhizum, cultivated under controlled conditions, against Giardia duodenalis, Trichomonas gallinae, and Leishmania infantum. Results showed broad-spectrum activity, particularly from non-polar extracts and EOs, suggesting that lipophilic compounds, especially germacrone, are key contributors to the observed effects. Germacrone exhibited strong activity and selective toxicity. Structural analogues of germacrone showed reduced efficacy, highlighting the importance of its specific chemical structure. Morphological analyses revealed parasite-specific responses to germacrone, contrasting with the more destructive effects of metronidazole and amphotericin B. The findings support G. macrorrhizum as a promising source of natural antiprotozoal agents and justify further investigation into its bioactive compounds and mechanisms of action.

Explore related subjects

microbiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Marcos-Herraiz, S., Irisarri-Gutierrez, M. J., Carrion, J., Azami Conesa, I., Suarez Lombao, R., Navarro-Rocha, J., Quilez, J. F., Fernandez Barrero, A., Ochoa, E., Gonzalez Coloma, A., Gomez Munoz, M. T., Bailen, M.. 2025-10-03. Activity of Geranium macrorrhizum extracts, essential oils and their main components against three relevant flagellated protozoa. https://doi.org/10.1101/2025.10.03.680318

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

pTRIP, a novel integration plasmid for Listeria monocytogenes

In the past decades, several tools to genetically modify the human pathogen Listeria monocytogenes were developed. Here, we constructed a new integrative plasmid system for L. monocytogenes named pTRIP, for treB insertion plasmid. pTRIP is a vector which stably integrates into the treB locus of the wild type EGD-e. This locus encodes the sole trehalose-specific EIIB and EIIC component of a phosphotransferase system. Successful integration leads to the disruption of treB and thus, to an inability of the resulting L. monocytogenes strains to grow on trehalose as sole carbon source. Due to integration through double homologous recombination, it is the first integrative system which does not require antibiotic selection pressure. To assess functionality of the pTRIP system, prfA and its native promoter region were integrated into the treB locus of a {Delta}prfA strain. Complementation was confirmed in 78% of the isolated clones, indicating successful integration of prfA into the treB locus. We further constructed derivatives of pTRIP harboring the constitutive Pp60 (pTRIP1) and the inducible Prha (pTRIP2) promoter to further expand application possibilities. Microscopic analyses confirmed the functionality of both promoter constructs and showed dose-dependent induction for Prha. pTRIP is an efficient tool for stable gene expression as well as functional studies and expands genetic modification possibilities for L. monocytogenes.

microbiology↗

bioRxiv2026

A rational design strategy and validation for protease-resistant fusion-inhibitor antiviral peptides

Peptide-based fusion inhibitors are promising pharmaceuticals in the fight against enveloped viruses relying on membrane fusion for host infection. However, peptide therapeutic applications have long been hindered by their poor stability in vivo. Here, we discovered that peptide inhibitors with the wildtype sequence of the heptad repeat 2 (HR2) domain of the SARS-CoV-2 spike protein are efficiently cleaved by Transmembrane Protease, Serine 2 (TMPRSS2), a key protease involved in the SARS-CoV-2 virus-cell fusion pathway. We then identified the corresponding cleavage sites and designed three protease-resistant peptides using ranking based on deep mutational scanning and natural occurrence. The three candidates all exhibit inhibitory activity in a cell-cell fusion assay. A high-resolution cryo-EM structure of the top candidate, HR2-NHN, bound to its HR1 target reveals the molecular basis for its potent activity. The top candidate of the cell-based screening assay significantly improved efficacy relative to the wildtype peptide when administered 12 h before infection in both an authentic virus-cell infection assay and a mouse assay. More broadly, our results suggest that the design strategies for protease-resistant peptides could be applied to a broad spectrum of other enveloped viruses and pave the way for the development of safe, prophylactic antivirals that can be administered before exposure.

microbiology↗

bioRxiv2026

Host soluble inositol phosphate signaling promotes coronavirus replication

Coronaviruses rely extensively on host pathways for replication, making host-directed therapies an attractive strategy for broad-spectrum antivirals with reduced risk of viral resistance. Here we identify the host soluble inositol phosphate pathway as a previously unrecognized dependency for coronavirus infection. Genetic or pharmacologic inhibition of several kinases in this pathway markedly suppresses replication of both alpha- and betacoronaviruses, while increasing pathway activity promotes viral replication. We developed UNC7844, a potent multi-target inhibitor of these kinases, which reduces coronavirus replication by more than four orders of magnitude in cultured cells and suppresses coronavirus infection in mice. Mechanistically, UNC7844 suppresses inositol (pyro)phosphates production, disrupts phosphoinositide homeostasis, and impairs late endosomal dynamics, blocking early post-entry steps required for viral genome release and replication. Together, our findings establish the soluble inositol (pyro)phosphate pathway as an important regulator of coronavirus infection and highlight its inhibition as a promising host-directed antiviral strategy.

microbiology↗