Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study

• Published in: Journal of molecular modeling Vol. 27; no. 8; p. 222
• Main Authors: Morgon, Nelson H., Grandini, Giulia S., Yoguim, Maurício I., Porto, Caio M., Santana, Lucas C., Biswas, Srijit, de Souza, Aguinaldo R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2021; Springer Nature B.V
• Subjects: Angiotensin-Converting Enzyme 2 - metabolism; Antiviral Agents - metabolism; Antiviral Agents - pharmacology; Attenuation; Binding Sites; Biological activity; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Drugs; Enantiomers; Fluorine; Host-Pathogen Interactions; Humans; Kinetics; Linezolid - metabolism; Linezolid - pharmacology; Molecular docking; Molecular Docking Simulation; Molecular Medicine; Original Paper; Protein Binding; Protein Conformation; Proteins; Receptors, Virus - metabolism; SARS-CoV-2 - drug effects; SARS-CoV-2 - pathogenicity; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; Structure-Activity Relationship; Theoretical and Computational Chemistry; VIII Symposium on Electronic Structure and Molecular Dynamics – VIII SeedMol; Virus Internalization - drug effects; Linezolid; SARS-CoV-2; Molecular docking
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-021-04828-8

The crescent evolution of a global pandemic COVID-19 and its respiratory syndrome (SARS-Cov-2) has been a constant concern (Ghosh 2021 ; Khan et al. 2021 ; Alazmi and Motwalli 2020 ; Vargas et al. 2020 ). The absence of a proven and effective medication has compelled all the scientific community to search for a new drug. The use of known drugs is a faster way to develop new therapies. Molecular docking is a powerful tool (Gao et al. J Mol Model 10: 44–54, 2004 ; Singh et al. J Mol Model 18: 39–51, 2012 ; Schulz-Gasch and Stahl J Mol Model 9:47–57, 2003 ) to study the interaction of potential drugs with SARS-CoV-2, Alsalme et al. ( 2020 ) and Sanders et al. ( 2020 ) spike protein as a consequence the main goal of this article is to present the result of the study of an interaction between ( R and S )-Linezolid with receptor-binding domain (RBD) of SARS-Cov-2 spike protein complexed with human Angiostensin-converting enzyme 2 (ACE2) (6vW1 - from PDB). The Linezolid enantiomers were optimized at B3LYP/6-311++G(2d,p) level of theory. Molecular docking of the system ( S )-Linezolid⋯ RBD ⋯ACE2 and ( R )-Linezolid⋯ RBD ⋯ACE2 was performed, the analysis was made using LigPlot+ and NCIplot software packages, to understand the intermolecular interactions. The UV-Vis and ECD of the complexes - ( R and S )-Linezolid⋯ RBD ⋯ACE2 were performed in two layers with DFT/6-311++G(3df,2p) and DFT/6-31G(d), respectively. The results showed that only the ( S )-Linezolid had a stable interaction with − 8.05 kcal.mol − 1 , whereas all the R -enantiomeric configurations had positive values of binding energy. The ( S )-Linezolid had the same interactions as in the ( S )-Linezolid ⋯ Haluarcula morismortui Ribosomal system, where it is well-known the fact that the latter has biological activity. A specific interaction on the fluorine ring justified an attenuation on the ECD signal, in comparison to isolated species. Therefore, some biological activity of ( S )-Linezolid with SARS-CoV-2 RBD was expected, indicated by the modification of its ECD signal and justified by a similar interaction in the S -Linezolid⋯ Haluarcula marismortui Ribosomal system.