Binding of Chloroquine to Whey Protein Relieves Its Cytotoxicity while Enhancing Its Uptake by Cells

Abstract

Chloroquine (CQ) is a famous medicine for treatment of diseases including malaria and pneumonia caused by COVID-19, but gastrointestinal disorder caused by its oral administration is a great concern. Milk is usually recommended to be taken with CQ to reduce such effect. However, the mechanism underlying this phenomenon remains unknown. Here, we found that β-lactoglobulin (β-LG), α-lactalbumin (α-LA), bovine serum albumin (BSA), and lactoferrin (LF) in whey proteins were able to interact with CQ to form complexes as suggested by fluorescence resonance energy transfer (FRET) and molecular docking. Indeed, the crystal structure revealed that β-LG is bound to CQ through hydrophobic interactions and hydrogen bonding with a ratio of 1:1. Consequently, the formation of these protein−CQ complexes not only reduced the cytotoxicity of chloroquine to the stomach and gut cells but also facilitated its uptake by cells. This work gave an example to understand the relationship between food and drug.

Natural Products and Nanotechnology Against Coronavirus Disease 2019

“…The Food Drug Administration approved chloroquine and hydroxychloroquine for emergency use in late March. The main mechanism of action is that entering lung cells can be activated by TMPRSS-2 ( Lobo-Galo et al, 2021 ; Yao et al, 2021 ). Although some concerns regarding chloroquine remain due to the side effects caused by the drug dosage, the subsequent optimization of loading based on nanotechnology will likely result in improved functionality and efficacy of chloroquine or chloroquine in the treatment of COVID-19 [ Table 1 ( Borba et al, 2020 ; Duvignaud et al, 2020 ; Group et al, 2020 ; Liu et al, 2020 ; Panda et al, 2020 ; Tirupakuzhi Vijayaraghavan et al, 2020 ; Weehuizen and Hoepelman, 2020 ; Abd-Elsalam et al, 2021 ; Gautret et al, 2021 ; Rea-Neto et al, 2021 ; Thakar et al, 2021 )].…”

Selective Detection of Chloroquine in Human Urine with Application at the Point-of-Care

“…Owing to the effectiveness and long-term use of chloroquine for treating malaria, many analytical approaches such as mass spectroscopy, 13 high-performance liquid chromatography (HPLC), 14 UV-VIS, 15 fluorescence spectroscopy 16 and electrochemical methods [17][18][19][20] have been developed for the detection of CQ. While HPLC and mass spectroscopy routinely provide high reproducibility and low detection limits for CQ quantification, they are lab-based, benchtop techniques which are both expensive and requires trained personnel to perform.…”