## 2 Materials and Methods
### Pharmacokine Features-ADMT  
Prediction of pharmacokinetics plays a vital role in the optimization of drug dosages, identification of potential drug interactions, and assessment of toxicity, thereby preventing setbacks in the late stages of drug development [32]. This process encompasses the evaluation of drug absorption, distribution, metabolism, and toxicity (ADMT) within the body. To ensure the pharmacokinetic (PK) properties of our compounds in comparison to the control drug, lecovirimat, we conducted thorough testing of their ADMT characteristics.  
The utilization of pre-ADMET v2.0 server [28], has enhanced prediction accuracy while providing a user-friendly interface. These servers enable us to predict and access data from previous in vitro and in vivo assays compiled from diverse databases. The web server facilitates comprehensive access to clinical trials pertaining to small molecules and peptides, along with bioassays, chemical registration, and analytical techniques such as nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Leveraging various algorithms and models, these platforms generate predictions. The employed ADMT parameters were as follows:  
* The evaluation of caco-2 cell permeability (nm/s) serves as a means to determine the ability of a potential drug to traverse the intestinal epithelium and enter the bloodstream. Generally, a drug is deemed orally available if it exhibits high permeability [33].
* Human intestinal absorption (HIA %) is a significant parameter used to predict the bioavailability of a drug following oral administration. Higher HIA values signify effective absorption, indicating a greater likelihood of the drug attaining therapeutic concentrations within the systemic circulation [28].
* P-glycoprotein (P-gp) is a protein that functions as an efflux pump present in the cell membranes of the liver, kidneys, and intestines. Its primary role within the cell is to eliminate undesired substances or drugs in a non-specific manner, thereby reducing their accumulation [34].
* Blood-brain barrier penetration involves a complex network of endothelial cells that serve the crucial function of safeguarding the brain against the entry of potentially harmful substances, such as toxins, into the central nervous system [35].
* The MDCK (Madin-Darby Canine Kidney) cell permeability, measured in nm/s, represents an epithelial cell line derived from the kidney of female canines. It serves as a valuable model for studying the transport of drugs across the intestinal epithelium [36].
* Plasma protein binding (%) is a measurement that indicates the extent to which drugs bind to proteins present in the plasma, such as albumin and globulin. This measurement is utilized to estimate drug distribution and assess drug-drug metabolism in relation to protein binding [37].
* Cytochrome P450 enzymes (CYPs) are predominantly located in the liver and are also present in tissues such as the kidneys and lungs. These enzymes play a vital role in metabolizing a wide range of endogenous substances (lipid metabolism) as well as exogenous compounds (drugs, toxins, and carcinogens). In our evaluation, we assessed the activity of key CYPs involved in drug metabolism, including CYP2C19, CYP2C9, CYP3A4, CYP2D6 [38].
* In terms of toxicity assessment, our compounds underwent Ames tests to evaluate their mutagenic potential [39]. Additionally, to ascertain their carcinogenicity, carcinogenicity prediction was performed using mice and rats as model organisms, owing to their genetic and physiological resemblance to humans. In order to assess cardiac safety, we predicted the inhibitory capacity of the human ether-related gene (HERG) channel, which is a voltage-gated potassium channel crucial for regulating the cardiac repolarization process [40].