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

Author(s)

Morgon, Nelson H. ^[1] ; Grandini, Giulia S. ^[2] ; Yoguim, Mauricio I. ^[2] ; Porto, Caio M. ^[1] ; Santana, Lucas C. ^[1] ; Biswas, Srijit ^[3] ; de Souza, Aguinaldo R. ^[2]

Affiliation

^[1] Univ Estadual Campinas, Inst Chem, Dept Phys Chem, BR-13083970 Campinas, SP - Brazil

^[2] Sao Paulo State Univ, Dept Chem, Sch Sci, BR-17033360 Bauru, SP - Brazil

^[3] Univ Calcutta, Dept Chem, 92 APC Rd, Kolkata 700009 - India

• Document type: Journal article
• Source: Journal of Molecular Modeling; v. 27, n. 8 AUG 2021.
• Web of Science Citations: 1

Abstract

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 center dot center dot center dot RBD center dot center dot center dot ACE2 and (R)-Linezolid center dot center dot center dot RBD center dot center dot center dot 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 center dot center dot center dot RBD center dot center dot center dot 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 center dot center dot center dot Haluarcula marismortui Ribosomal system. (AU)

• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/22338-9 - Study of the interaction between drugs and human serum albumin (HSA) based on computer simulation, DFT and TDDFT, experiments of electronic circular dichroism, ECD, and determination of the bond formation constant
• Grantee: Aguinaldo Robinson de Souza
• Support Opportunities: Regular Research Grants