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Cell membrane chromatography for the analysis of the interaction between chloroquine and hydroxychloroquine with ACE2 receptors.

ABSTRACT: The recent emergence of the novel pathogenic coronavirus disease 2019 (COVID-19) is responsible for a worldwide pandemic. In sight of this, there has been growing interest in the use of chloroquine (CQ) and hydroxychloroquine (HCQ) as potential treatments. In this study, we use angiotensin converting enzyme 2 (ACE2) over-expressed cell membrane chromatography (CMC) to study the interaction of CQ and HCQ with ACE2 receptor. Both CQ and HCQ were retained on the ACE2/CMC column. Then we analyzed the binding character of CQ and HCQ to ACE2 by CMC frontal analysis, ionic force investigation and competitive binding experiment. Results showed that CQ and HCQ KD values obtained from the CMC frontal analysis method were 8.22(±0.61) × 10^-7 M and 11.70(±2.44) × 10^-7 M. Compare to CQ, HCQ has the weaker affinity with ACE2. The action force of CQ, HCQ and ACE2 is mainly ionic force. CQ and HCQ have different degrees of competitive binding relationship with ACE2. Our study revealed the interaction of CQ and HCQ with ACE2 receptor, which provides new insights for the use of CQ and HCQ in the treatment of COVID-19. Moreover, this biomimetic drug screening method is expected to open the door for rapid targeting and separating bioactive ingredients active towards ACE2 receptor.

SUBMITTER: Fu J

PROVIDER: S-EPMC7700726 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Cell membrane chromatography for the analysis of the interaction between chloroquine and hydroxychloroquine with ACE2 receptors.

Fu Jia J Jia Qianqian Q Zhou Huaxin H Zhang Liyang L Wang Saisai S Liang Peida P Lv Yanni Y Han Shengli S

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 20201129

The recent emergence of the novel pathogenic coronavirus disease 2019 (COVID-19) is responsible for a worldwide pandemic. In sight of this, there has been growing interest in the use of chloroquine (CQ) and hydroxychloroquine (HCQ) as potential treatments. In this study, we use angiotensin converting enzyme 2 (ACE2) over-expressed cell membrane chromatography (CMC) to study the interaction of CQ and HCQ with ACE2 receptor. Both CQ and HCQ were retained on the ACE2/CMC column. Then we analyzed th ...[more]

PMID: 33310480

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Project description:BackgroundChloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs).MethodsWe systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes.ResultsThe literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n = 1,077 CQ, n = 1,060 placebo), while the trials for HCQ involved 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non-COVID-19 patients, HCQ-treated non-COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study.ConclusionsTaken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9).RegistrationThe meta-analysis was registered on OSF (https://osf.io/jm3d9).

Dataset Information

Cell membrane chromatography for the analysis of the interaction between chloroquine and hydroxychloroquine with ACE2 receptors.

Publications

Cell membrane chromatography for the analysis of the interaction between chloroquine and hydroxychloroquine with ACE2 receptors.

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