## 1 Introduction  
The herpes simplex virus (HSV) is a prevalent, human DNA virus belonging to the Herpesviridae family, which can remain dormant in the neurons of infected people for life. Periodically, it can become active again, leading to recurrent infections, shedding of the virus, and transmission to new hosts. HSV-2 typically affects the genital and mucosal areas. In some cases, infections can be serious, resulting in significant health problems and, in rare instances, even leading to conditions like viral encephalitis, meningitis, or blindness [1]. The virus is endemic worldwide and has no effective vaccines or prophylaxis that provide complete protection or immunity [2]. According to the World Health Organization, about 417 million people aged 15-49 have HSV-2 infections [3]. The available pharmaceuticals for treating viral infections are relatively restricted. The conventional approach to treating herpesvirus infections in humans involves antiviral chemotherapy. Presently, there are approximately 11 authorized drugs designed for this purpose [4]. The most commonly used one is the nucleoside analog acyclovir and its derivatives [4; 5]. However, continuous therapy can result in the emergence of resistant strains [4; 6]. This fact underscores the need for the creation of novel antiviral compounds. In this context, natural products have been reported as promising antiviral agents [7]. Plant antiviral therapy offers advantages over currently utilized chemotherapeutic agents since they tend to have fewer adverse effects. Additionally, their complex chemical composition often hinders the development of resistant strains [8]. Plants are widely known for their powerful antiviral effects. It has been demonstrated by some researchers that phytocompounds derived from various plants, such as polyphenols, have antiherpetic activities. Specifically, polyphenol-rich extracts have been shown to have anti-herpetic activities [9]. In recent studies, it has been found that caffe acid and its derivatives, and kaempfer, can inhibit the activity of HSV [10]. Rutin, a flavonoid glycoside generally found in many plants, is highly effective against HSV-1, HSV-2, and other viruses, and is among the bioactive compounds produced by different plant species [11]. _Sambucus nigra_ and _Sambucus ebulus_, commonly known as Black elder and Dwarf elder, respectively, belong to the Adoxaceae family (previously Caprifoliaceae). SN is widespread across Europe, west and central Asia, northern Africa, and North America [12]. Ethnobotanically, it is one of the most commonly used medicinal plants worldwide, and it is commonly used for both food and medicine [12; 13]. SE is a perennial plant or bush and is mainly widespread across southern and central Europe, Southwest Asia, and northwest Africa [14]. The fruits and flowers of SN and SE are rich in bioactive phenolics including phenolic acids, flavonoids, and anthocyanins, which underlie their health benefits, supported by strong scientific evidence [14; 15; 16]. They act as antioxidants, reduce inflammation, modulate the immune system, demonstrate activity against cancer, and exhibit a broad spectrum of antiviral properties [14; 15; 16; 17; 18; 19; 20; 21; 22; 23]. Extracts and products from SN fruits that exhibit antiviral activity are currently some of the most significant highlights of research [24]. SN fruit extracts and flower infusions have demonstrated effectiveness in alleviating symptoms of a variety of viral infections, independently of their mechanisms [12]. In vitro studies have indicated that Sambucol (extract prepared from fruits) significantly inhibits HSV-1, even against strains resistant to different conventional antiviral drugs [25]. In addition, in vitro experiments have demonstrated the effectiveness of Sambucol as an antiviral agent against HIV [26]. An infusion comprising flowers from _S. nigra_, aerial parts of _Hypericum perforatum_, and roots of _Saponaria officinalis_ inhibited HSV-1 in vitro, and influenza A and B, both in vitro and in animal models [27; 28; 29].