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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Journal of Molecular Modeling; v. 27, n. 8 AUG 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 13/08293-7 - CECC - Centro de Engenharia e Ciências Computacionais
• Beneficiário: Munir Salomao Skaf
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/22338-9 - Estudo da interação entre fármacos e a albumina do soro humano (HSA) baseado em simulação computacional, DFT e TDDFT, experimentos de dicroísmo circular eletrônico, ECD, e determinação da constante de ligação
• Beneficiário: Aguinaldo Robinson de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular