To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38–7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein’s binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
【저자키워드】 COVID-19, docking, Molecular simulation, quaternary ammonium, amphiphile, k21 spike, fit pose, 【초록키워드】 SARS-CoV-2, Human, drugs, molecular docking, immune system, virus, Spike protein, binding site, ACE-2, Probability, spike receptor-binding domain, respiratory, binding, Concentration, Ammonium, reduction, two-dimensional, Viral protein, complex, lung tissue, human host, root, assumption, negative, PDB, Arm, immunological, fluctuation, bind, square, shown, conducted, less, determine, downloaded, entry of SARS-CoV-2, immunogenic potential, negative and positive, the SARS-CoV-2, 【제목키워드】 drug, Simulation, dynamic,