## 1 Introduction  
Emodin (1,3,8-trihydroxy-6-methylanthraquinone; Figure 1A) is a natural plant-derivative anthraquinone with its common name derived from the Himalayan rhubarb (_Rheum emodi_). Emodin is particularly abundant in the roots of the Chinese rhubarb (_Rheum palmatum_), rhubarb (_Rheum officiale_), buckthorn of the _Rhamus_ genus, knotweed and knotgrass (_Polygonum cuspidatum_ and _multiforum_) as well as Hawaii 'au'auko'i cassia seeds or coffee weed (_Semen cassia_). Emodin-rich Chinese rhubarb, knotweed and knotgrass have been used for centuries in traditional Chinese medicine. Moreover, emodin constitutes one of the major active principles of the antiviral formulation Lianhua Qingwen [1]. Emodin can also be abundant in certain foods upon mold contamination being produced as a secondary fungi metabolite produced by _Aspergillus_, _Penicillium_, _Talarmyces_, _Pyrenochaeta_ and _Pestalotiopsis_ genera [2]. In this regard, emodin has been recently included in the group of emerging mycotoxins [2] and growing evidence of its occurrence in food is being collected [3, 4]. Bioactivity of emodin involves both health-protective and toxic effects. Anticancer, anti-inflammatory, antibacterial and antiviral activities are amongst its potential beneficial properties. In contrast, toxic effects include genotoxicity, nephrotoxicity, hepatotoxicity and reproductive toxicity [5; 6]. Nonetheless, the mechanisms of action underpinning these activities remain to be investigated to provide a thorough characterization of emodin's bioactivity as well as to inform about the consumption of emodin-containing plants. With regard to antiviral properties, in vitro evidence has shown that emodin inhibits the interaction between the etiological agent of the human severe acute respiratory syndrome (SARS), the coronavirus referred to as SARS-CoV-1, and host cells target receptor [7]. Several molecules, including broad-spectrum antiviral drugs, have been described as promising to counteract SARS-CoV-1 infection [8]. These compounds act through diverse mechanisms of action and prevent either viral entry into host cells or viral replication and release [9]. Moreover, a host of natural compounds have also been identified and tested in vitro resulting in promising antiviral activity against SARS-related coronavirus [10]. Among these, emodin was found to block the interaction between the SARS-Cov-1 spike (S) protein and the human target receptor angiotensin I converting enzyme 2 (ACE2) limiting host cell invasion [7]. Emodin was also found to inhibit the 3a protein ion channel activity which may provide a basis for the observed reduction in the virus release [11]. This evidence suggests a multi-target action of emodin highlighting the anthraquinone scaffold as a potential starting point to develop candidate antiviral agents with pharmacological activities. However, the poor mechanistic understanding of emodin's antiviral action at the molecular level prevents the rational identification of emodin derivatives or natural analogues as a potential candidate compounds for the development of more effective antiviral congeners. In late 2019, a new coronavirus (SARS-CoV-2) was identified as the agent causing a novel coronavirus-related disease (COVID-19) [12]. The analogies between SARS-CoV-2 and the phylogenetically related SARS-CoV-1 led to further assessment of those molecular scaffolds that counteract with SARS-CoV-1. Specifically, emodin has emerged as a possible candidate for drug formulations targeting SARS-CoV-2 [13]. Nonetheless, as mentioned above, the lack of understanding of emodin's mechanisms of action limits its potential and rational use as a model compound to design or discover efficient pharmacologically active analogues. In the last two decades, computational methods, also as stand-alone studies, supported the characterization of small molecules' activity as well as proteins behavior, and the use of molecular modeling approaches led to advances in their mechanistic understanding [14; 15; 16].