Human Adenovirus belongs to the family of Adenovirus and is a non-enveloped double-stranded DNA virus. It was first isolated from human adenoid tissue culture by Rowe et al. in 1953. Currently, human adenovirus is divided into 6 subgroups and 52 serotypes. Different serotypes of adenovirus can cause multiple diseases in different body parts, such as gastroenteritis, conjunctivitis, cystitis, rhinitis, pharyngitis, and diarrhea [1], [2]. Most of the symptoms of HAdV infections are mild and self-limited. However, People with low immunity, such as children and patients after organ transplantation may have a higher infection rate than ordinary people [3], [4]. Although studies at home and abroad indicate that adenovirus is not the main pathogen of community-acquired pneumonia in adults, it can cause severe respiratory symptoms in people with low immunity [5], [6], [7], [8], [9]. More importantly, there is currently no specific treatment for HAdV infections, as well as the high fatality rate and poor prognosis arouse high clinical attention. At present, there is no targeted treatment for adenovirus infection. Patients with severe infections usually take anti-inflammatory therapy combined with immunoglobulin for supportive treatment [10], [11].

In order to study anti-adenoviral drugs, exploring the pathogenic mechanism of adenovirus is the primary condition. After the HAdV enters the host cells, the virus enters the nucleus for DNA replication and induces extensive recombination of DNA in the nucleus. The pathogenic mechanism of the virus may be to enhance the DNA replication of the virus by destroying the original DNA structure of the nucleus, thereby inducing cell death and increasing the virus load. Based on previous research, cidofovir is often used for the treatment of adenoviral pneumonia in clinical application [12], [13]. However, cidofovir has certain nephrotoxicity, especially for infants and children, which may cause more serious adverse reactions. Therefore, the clinical application of cidofovir in the treatment of adenovirus pneumonia is lack of standardization [14], [15], [16], [17]. The emphasis of the development of new anti-adenoviral drugs is to improve the antiviral efficiency of the drugs and reduce the adverse reactions caused by the drugs to meet the exact clinical needs.

Selenium (Se) is a trace element in the human body and plays an important role in regulating enzyme activity and metabolism [18]. Studies have shown that the daily selenium content of the human body through dietary intake is 400 μg/L, while the selenium content in blood of normal people is 139 μg/L [19], [20]. Different forms of selenium have different metabolic pathways, and the toxic effects of selenium are strictly dependent on concentration and chemical substances. Selenium in supranutritional doses exhibits specific killing of tumor cells through associated toxicity and resistance to viral infections through antioxidant activity. Furthermore, the selenoprotein in the human body controls several important biological metabolic pathways [21]. Se plays an important role in anti-oxidation, redox signal transduction, and redox homeostasis. Most of the biological activity of selenium is achieved by converting it into a rare amino acid, selenocystine [22]. The functions of selenoproteins include participating in the regulation of intracellular redox signals, thereby maintaining redox homeostasis, and participating in the metabolism of some hormones [23]. Selenium and selenoproteins are widely involved in the pathogenic and therapeutic mechanisms of diseases in different systems. Selenoproteins play a major role in cardiovascular diseases by regulating the destructive effect of ROS, reducing cell damage and mitochondrial dysfunction caused by ROS [24]. Selenium is involved in TRP channel regulation, Ca2+ signaling in the nervous system, and has a protective role in apoptosis and mitochondrial oxidative stress-induced peripheral pain [25]. HIV infection can lead to increased oxidative stress in CD4+ T lymphocytes, which interferes with the metabolism of selenium and the composition of the selenoproteome. According to some research, a lack of selenium may increase the probability of infection with the respiratory virus [26]. Virus infection can cause a series of body damage, and oxidative stress is one of its signs. Some studies have shown that the increase in ROS can in turn enhance virus replication, leading to a vicious circle of infection [27], [28]. In recent years, the antiviral and antitumor activity of selenium-containing drugs has become a research hotspot [29], [30], [31], [32]. The excellent biological activity of SeC has gradually attracted attention and been applied in the medical field. In addition to the excellent antioxidant effect of SeC, some research proved that SeC could effectively reduce cell apoptosis caused by DNA damage [33]. Specific treatment for adenovirus is a new clinical direction, and there is an urgent need to find new anti-adenovirus drugs. SeC has a certain foundation of research in repairing body damage, protecting and maintaining body function, anti-tumor treatment, and antiviral effect, which affirms its excellent biological activity and antioxidant effect [34], [35], [36]. Thus, SeC may have good application prospects in the treatment of adenovirus. Based on the excellent biological activity of SeC, our research hypothesizes that SeC exhibits excellent anti-HAdV-14 ability. The purpose of this study is to explore whether SeC can inhibit HAdV-14 infection and its antiviral mechanism.