The Malaria Box molecules: a source for targeting the RBD and NTD cryptic pocket of the spike glycoprotein in SARS-CoV-2

Context SARS-CoV-2, responsible for COVID-19, has led to over 500 million infections and more than 6 million deaths globally. There have been limited effective treatments available. The study aims to find a drug that can prevent the virus from entering host cells by targeting specific sites on the v...

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Published in:Journal of molecular modeling 2024-07, Vol.30 (7), p.217, Article 217
Main Authors: Otazu, Kewin, Olivos-Ramirez, Gustavo E., Fernández-Silva, Pablo D., Vilca-Quispe, Julissa, Vega-Chozo, Karolyn, Jimenez-Avalos, Gabriel M., Chenet-Zuta, Manuel E., Sosa-Amay, Frida E., Cárdenas Cárdenas, Reyna G., Ropón-Palacios, Georcki, Dattani, Nike, Camps, Ihosvany
Format: Article
Language:English
Subjects:
Antiviral Agents - chemistry
Antiviral Agents - pharmacology
Binding energy
Binding Sites
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Computer Appl. in Life Sciences
Computer Applications in Chemistry
COVID-19 - virology
COVID-19 Drug Treatment
Glycoproteins
Humans
Malaria
Molecular docking
Molecular Docking Simulation
Molecular dynamics
Molecular Dynamics Simulation
Molecular Medicine
Original Paper
Protein Binding
Protein Domains
Proteins
SARS-CoV-2 - drug effects
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Spike Glycoprotein, Coronavirus - chemistry
Spike Glycoprotein, Coronavirus - metabolism
Stability
Theoretical and Computational Chemistry
Viruses
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Summary:Context SARS-CoV-2, responsible for COVID-19, has led to over 500 million infections and more than 6 million deaths globally. There have been limited effective treatments available. The study aims to find a drug that can prevent the virus from entering host cells by targeting specific sites on the virus’s spike protein. Method We examined 13,397 compounds from the Malaria Box library against two specific sites on the spike protein: the receptor-binding domain (RBD) and a predicted cryptic pocket. Using virtual screening, molecular docking, molecular dynamics, and MMPBSA techniques, they evaluated the stability of two compounds. TCMDC-124223 showed high stability and binding energy in the RBD, while TCMDC-133766 had better binding energy in the cryptic pocket. The study also identified that the interacting residues are conserved, which is crucial for addressing various virus variants. The findings provide insights into the potential of small molecules as drugs against the spike protein. Graphical abstract
ISSN:1610-2940
0948-5023
0948-5023
DOI:10.1007/s00894-024-06006-y