Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19
Metadatos
Mostrar el registro completo del ítemEditorial
Frontiers
Materia
TMPRSS2 COVID-19 Molecular docking Casiopeina-like metallodrugs Copper DFT Casiopeina analogs
Fecha
2023-01-26Referencia bibliográfica
Vazquez-Rodriguez S... [et al.]. (2023), Interaction of copper potential metallodrugs with TMPRSS2: A comparative study of docking tools and its implications on COVID-19. Front. Chem. 11:1128859. doi: [10.3389/fchem.2023.1128859]
Patrocinador
100108444-VIEP, 100256733-VIEP, and 100233622-VIEP; PRODEP Academic Group BUAP-CA-263 (SEP, Mexico); Ministerio de Universidades and Funds Next-Generation for the Margarita Salas contract 401 (Spain); CNPq (Brazil) (309029/2018-0)Resumen
SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. For the virus to
enter the host cell, its spike (S) protein binds to the ACE2 receptor, and the
transmembrane protease serine 2 (TMPRSS2) cleaves the binding for the fusion.
As part of the research on COVID-19 treatments, several Casiopeina-analogs
presented here were looked at as TMPRSS2 inhibitors. Using the DFT and
conceptual-DFT methods, it was found that the global reactivity indices of the
optimized molecular structures of the inhibitors could be used to predict their
pharmacological activity. In addition, molecular docking programs (AutoDock4,
Molegro Virtual Docker, and GOLD) were used to find the best potential
inhibitors by looking at how they interact with key amino acid residues (His296,
Asp 345, and Ser441) in the catalytic triad. The results show that in many cases, at
least one of the amino acids in the triad is involved in the interaction. In the best
cases, Asp435 interacts with the terminal nitrogen atoms of the side chains in a
similar way to inhibitors such as nafamostat, camostat, and gabexate. Since the
copper compounds localize just above the catalytic triad, they could stop substrates
from getting into it. The binding energies are in the range of other synthetic drugs
already on the market. Because serine protease could be an excellent target to stop
the virus from getting inside the cell, the analyzed complexes are an excellent place
to start looking for new drugs to treat COVID-19.