## 1 Introduction  
The number of Coronavirus Disease (COVID-19) cases continues to rise daily. According to the World Health Organization (WHO), as of December 2022, there were 639,132,486 confirmed cases of COVID-19 across 216 countries, resulting in 6,614,082 death [1]. As the virus evolved, SARS-CoV-2 mutated into various variants: Alpha, Beta, Gamma, Delta, Omicron, Lambda, and Mu [2]. COVID-19 is caused by the severe acute respiratory syndrome virus (SARS-CoV-2). Clinical symptoms of COVID-19 include an increased inflammatory response, respiratory disorders, multi-organ dysfunction syndrome, and significant thrombotic complications [3]. While 60% of infected cases recover after 28 days of hospital treatment, many patients continue to experience symptoms 3-12 weeks post-recovery, a condition known as Long COVID-19 syndrome [4]. Long COVID-19 is characterized by persistent symptoms that extend beyond 4 weeks following the onset of SAR-CoV-2 infection. During this phase, the transcription factor erythroid 2-related factor 2 (Nrf2) and the formation of inflammosomes play pivotal roles in developing Long COVID-19 [5]. DNA damage within infected cells inhibits the expression of Nrf2, which typically provides primary protection against oxidative stress (ROS). Excessive ROS production from SAR-COV-2 infection can disrupt the antioxidant system and cause widespread cellular damage if not counterbalanced by antioxidant production [6]. Maintaining ROS levels in homeostasis is crucial to prevent damage to DNA, proteins, and lipid structures. Under unfavorable conditions, ROS can activate transcription factors such as Nrf2. Upon activation, Nrf2 translocates into the nucleus and binds to the Antioxidant Response Element (ARE), activating genes crucial for antioxidant production [7]. Adequate antioxidant production is essential to mitigate cellular damage caused by ROS. Antioxidants are compounds capable of delaying, slowing, and preventing oxidation [8]. The body naturally combats oxidative stress through endogenous antioxidants. However, when free radicals surpass endogenous antioxidants, supplementation with exogenous antioxidants from food and medicines becomes necessary [9]. To date, no medication has been developed to alleviate the symptoms of Long COVID-19, which results from a disruption in antioxidant enzyme expression due to COVID-19 infection [10]. Exploring natural compounds, such as apigenin, for their therapeutic potential against Long COVID-19 highlights the significance of discovering therapeutic agents from natural sources [11]. Such discoveries hold promise for the development of effective treatments for Long COVID-19 and other oxidative stress-related conditions. In vitro studies have shown that apigenin, a flavonoid compound, possesses therapeutic properties such as antioxidant, anti-inflammatory, antidiabetic, anticancer, antidepressant, and neuroprotective effects [12]. A recent in silico study explored the potential of apigenin against Long COVID-19 using a 100-run molecular docking simulation (Autodock 4.2) of the Keep1-Nrf2 complex (PDB code 4L7B), resulting in a free energy value of \(-6.24\) kcal/mol. Apigenin demonstrated interactions with amino acid residues Ser602, Ser363, Ser508, and Ser555 [13]. Further research is needed to validate the predicted activity of apigenin as an anti-Long COVID-19 agent by binding to NRF2 using molecular dynamics simulation methods. Other studies have suggested that the antiviral effect of apigenin may be directly linked to suppressing the activity of SARS-CoV 3 CLpro [14]. Thus, apigenin intake, through a regular diet or supplements, may potentially mitigate chronic infection diseases such as COVID-19 [15]. Molecular dynamics is a computerized simulation used to examine microscopic interactions between molecules [16]. Using a physically known approach, this simulation allows atoms and molecules to interact over a specified period, providing insight into motion and interactions [17].