###### Abstract  
The leaves of _Ilex panguariensis_ (known as _Y_ebra mate), used as a popular beverage, are a very well-recognized plant material with various biological activities, including anaeleptic (because of caffeine), anti-obesity (phenolics, saponins), antimicrobial, and antiviral (phenolics, saponins). Here, the chemical compositions of the leaves of two European _Ilex_ species (\(\times\)_meservoae_ and _aquifolium_) with three varieties each were investigated. The terpenoid, saponin, and polyphenic fractions were submitted for LC-MS or GC-MS analysis against a standard Mate leaf. In addition, the aroma profiles of all the species were analysed using HS-SPME-Arrow prior to GC-MS analysis. All fractions were subjected to antiviral and cytotoxic assays. We found 86 compounds in all accessions, with limonene,linal, and \(p\)-cymene being predominant. There were minor similarities between the volatile compositions of the European and South American species. We found unsolic and oleanolic acid to be the main compounds in the terpenoid fraction. Mono-caffeoylquinic acids and di-caffeoylquinic acids were the main constituents of the polar fractions. About 180 compounds from the saponin group were tentatively identified, of which 9 and 3 were selected as distinctive markers for _I. meservae_ and _I. aquifolium_, respectively. Based on chemical screening _I. aquifolium_ Silver Queen was chosen as the source of terpenoid and saponin fractions and polyphenol extracts. The most substantial inhibition of cancer cell growth was observed with saponin in the case of the MCF7 (human breast cancer) cell line, while for LoVo and L929 cell lines (human colorectal cancer and reference mouse fibroblasts), it was slightly weaker. These results should be analysed further as a promising chemoprevention of colorectal and gastrointestinal cancers. Saponin and polyphenic extracts exhibited similar activities against HSV-1 and HAdV-5, with 4-log reduction in virus titres. This study focuses our attention on a field of potential antiviral formulations derived from European holly. _Ilex_; terpenoids; saponins; phenolic acids; antiviral activity; anticancer activity; cytotoxic activity 20242932313231323132313231323132313231323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132323132332313  
to have anti-cholesterol and antidiabetic effects [3]. Regular consumption of Yerba Mate improves body weight composition, appetite, and mood. Water extracts of this plant have a proven cytotoxic activity against several cancer lines, including colorectal [4], colon [5], liver, and colorectal adenocarcinoma (in the rat model) [6]. The ethyl acetate fraction of _I. paraguariensis_ inhibits _Herpes simplex_ virus Type 1 and Type 2 replication [7]. Polyphenol-rich extracts of _I. paraguariensis_ inhibited 3 CL protease in SARS-CoV-2 [8,9]. The biological activities of both extracts and fractions of European taxons of _Iex_ such as _I. aquifolium_ Aurea Marginata, Silver Queen, Handsworth New Silver; and _I. mesereae_ Blue Prince, Blue Girl, and Blue Princess were analysed. Our previous research showed excellent anti-cholesterol and hepatoprotective activities of water extracts of _I. aquifolium_ in Wistar rats [10]. Additionally, its terpenoid and saponin fractions positively affected metabolic parameters through the inhibition of ACAT-1 gene expression in the liver of Zucker rats (fa/fa); this can be helpful in the prevention of metabolic disorders [11]. Caffeoylquinic acids isolated from _I. pubescens_ (native to China) strongly inhibited neuraminidase of Influenza A virus by binding to Tyr100, Gln412, and Arg419, leading to inhibition of replication [12]. In addition, 3,4-di-O-caffeoylquinic acids isolated from _I. kaushue_ revealed activity in the initial phase of enterovirus A71 infection by directly targeting the virus particle and disrupting its attachment to host cells [13]. Saponins such as apprellosides isolated from _I.