Designing drugs that selectively target the entry proteins of the SARS-CoV-2 virus without affecting the normal function of similar entry proteins in human cells can be achieved by following a systematic approach within the constraints of medicinal chemistry principles. Here are the steps to achieve this:1. Identify the target protein: The primary entry protein of the SARS-CoV-2 virus is the spike S protein, which binds to the human angiotensin-converting enzyme 2 ACE2 receptor. The S protein-ACE2 interaction is crucial for viral entry into host cells.2. Study the protein structure: Obtain the crystal structure or use computational methods to predict the structure of the S protein and the ACE2 receptor. Analyze the binding interface between the S protein and ACE2 to identify key residues involved in the interaction.3. Design a selective inhibitor: Based on the structural information, design a small molecule or a peptide that selectively binds to the S protein, thereby inhibiting its interaction with the ACE2 receptor. The inhibitor should have high affinity and selectivity for the S protein, and not interact with other human proteins, especially those with similar structures.4. Apply medicinal chemistry principles: Optimize the inhibitor's physicochemical properties, such as lipophilicity, solubility, and hydrogen bonding, to ensure good bioavailability, cell permeability, and metabolic stability. Additionally, the inhibitor should have low toxicity and minimal off-target effects.5. Perform in silico screening: Use computational methods, such as molecular docking and molecular dynamics simulations, to predict the binding affinity and selectivity of the designed inhibitor for the S protein.6. In vitro testing: Test the designed inhibitor in vitro using biochemical and biophysical assays to confirm its binding affinity, selectivity, and inhibitory activity against the S protein-ACE2 interaction.7. In vivo testing: Evaluate the efficacy, safety, and pharmacokinetics of the inhibitor in animal models of SARS-CoV-2 infection.8. Optimization and lead development: Based on the results from in vitro and in vivo testing, further optimize the inhibitor's structure and properties to improve its potency, selectivity, and pharmacokinetic profile.9. Clinical trials: Once a lead compound is identified, proceed with clinical trials to assess its safety, efficacy, and optimal dosing in humans.By following these steps and adhering to medicinal chemistry principles, it is possible to design drugs that selectively target the entry proteins of the SARS-CoV-2 virus without affecting the normal function of similar entry proteins in human cells.