Comparative Study of Docking Tools for Evaluation of Potential Copper Metallodrugs and Their Interaction with TMPRSS2 Vázquez Rodríguez, Sergio Ramírez Contreras, Diego Noriega, Lisset García García, Amalia Sánchez-Gaytán, Brenda L. Meléndez, Francisco J. Filgueira de Azevedo, Walter Jr Castro, María Eugenia González-Vergara, Enrique COVID-19 molecular docking TPMRSS2 COVID-19 has caused over seven million deaths globally due to its high transmission rate. The virus responsible for the disease requires a transmembrane protease serine type II (TMPRSS2- 7MEQ) to infiltrate host cells and has been linked to several cancers, particularly prostate cancer. To investigate COVID-19 potential therapies, a series of Casiopeina-like copper complexes containing 1,10-Phenanthroline and amino acids were investigated as TMPRSS2 inhibitors. The molecular structures of twelve Phenanthroline copper complexes were calculated, and their global reactivity indices were analyzed using DFT and conceptual DFT methods. Three molecular docking algorithms were employed to identify the most effective inhibitors by examining their interactions with amino acid residues in the target protein’s catalytic activity triad (Asp345, His296, and Ser441). All complexes are docked above the catalytic site, blocking the interaction with substrates. The Phenanthroline complexes showed better interactions than the Bipyridine complexes, likely due to increased hydrophobic contacts. Analogs’ cationic nature and amino acids’ basic side chains bring them near the active site by interacting with Asp435. The top complexes in this study contain Ornithine, Lysine, and Arginine, making them promising alternatives for researching new drugs for COVID-19 and cancers like prostate cancer. 2024-12-10T11:32:54Z 2024-12-10T11:32:54Z 2024-10-30 journal article Vázquez Rodríguez, S. et. al. Inorganics 2024, 12, 282. [https://doi.org/10.3390/inorganics12110282] https://hdl.handle.net/10481/97820 10.3390/inorganics12110282 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI