title: Screening HIV-1 fusion inhibitors based on capillary electrophoresis head-end microreactor targeting to the core structure of gp41.
abstract: In this paper, we design a microreactor based on electrophoretically mediated microanalysis (EMMA) with capillary electrophoresis (CE) for screening HIV-1 inhibitors that bind to the N-terminal heptad repeat (NHR, N36) region. Initially, a test sample plug is loaded into a capillary filled with buffer solution followed by N36 peptide solution, and the two solutions simultaneously mix by diffusion. Then, voltage is applied, and the sample molecules pass through the N36 peptide zone. The active compounds combine with N36, leading to a loss in the peak height of the active compound. More than 100 traditional Chinese medicine extracts (TCME) were screened, and an extract of Pheretima aspergillum (E. Perrier) (L5) was identified as having potent inhibitory activity. The results showed that L5 could significantly inhibit the HIV-1JR-FL pseudotyped virus infection; the 50% effective concentration (EC50) of L5 was approximately 32.1±1.2μg/mL, and the 50% cytotoxicity concentration (CC50) value of L5 was 146.9±4.4μg/mL, suggesting that L5 had low in vitro cytotoxicity on U87-CD4-CCR5 cells. The new method is simple and rapid, is free of antibodies, and does not require tedious processes.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Internal Medicine ward, Jinzhou People's Hospital, 1 Chaoyang Street, Jinzhou 052260, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China. Electronic address: li75lin@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China. Electronic address: jiazm@fimmu.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Jia
mesh_terms: D065100:CCR5 Receptor Antagonists / Q000008:administration & dosage / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000032:analysis*; D019075:Electrophoresis, Capillary / Q000379:methods; D015700:HIV Envelope Protein gp41 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans
chemical_list: D065100:CCR5 Receptor Antagonists; D004365:Drugs, Chinese Herbal; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: Gp41; HIV-1 inhibitors; Microreactor; Six-helix bundles; Traditional Chinese medicines