Structural dynamics of chlorpromazine (CPZ) drug with dipalmitoylphosphatidylcholine (DPPC) lipid: a potential drug for SARS-CoV-2

Abstract

There is an urgent requirement for drug discovery and more importantly drug repositioning due to infectious new Severe Acute Respiratory Syndrome coronavirus 2. As per the recent report published in the journal L'Encéphale in May 2020, there is a planned ReCoVery Study examining the repurposing the chlorpromazine for the treatment of COVID-19. Here, we apply a combined Raman microspectroscopy and DFT-MD approach to investigate the structural dynamics of the Chlorpromazine (CPZ) drug with dipalmitoylphosphatidylcholine (DPPC) lipid bilayer, identifying the specific position of the drug in the DPPC lipid bilayer. The intensity ratios of the Raman peaks I₂₉₃₅/I₂₈₈₀, I₁₀₉₇/I₁₀₆₄ and I₁₀₉₇/I₁₁₂₉ are representative of the interaction of drugs with lipid alkyl chains and furnish conformation of lipid alkyl chains. Raman imaging microscopy for the study of the distribution of CPZ inside the lipid vesicles is reported. We also investigated the influence of order and disorder ratio in the CPZ on the DPPC liposomes prepared on phase transition temperature.

HIGHLIGHTS

• Drug–membrane interactions using micromolar concentrations of both lipid and drugs.

• Neuroleptic drug and DPPC vesicles composed of DPPC/drug mixtures reveal qualitative differences between the Raman spectra

• The temperature-controlled Raman microspectroscopic study has demonstrated that below phase-transition temperature, the fatty acid chains of the phospholipids are stiff and packed in a highly ordered array.

• DFT and MD simulations to understand molecular interactions, structural dynamics, and Raman spectra.

• Above phase-transition temperature, the chains are disordered and possess more motional freedom.

Communicated by Ramaswamy H. Sarma

Keywords:

• Raman
• dipalmitoylphosphatidylcholine
• Chlorpromazine
• COVID 19
• DFT and MD Simulations

Acknowledgments

Soni Mishra thanks Graphic Era Hill University for SEED financial support and Abhishek Kumar Mishra acknowledges the SEED grant (Year 2021) from UPES, Dehradun for computational resources.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

The author(s) reported there is no funding associated with the work featured in this article.