Molecular mechanism of the bitter taste of HIV/AIDS drugs and its inhibition

HIV/AIDS药物苦味及其抑制的分子机制

基本信息

批准号：
10548006
负责人：
MENG CUI
金额：
$ 19.63万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10548006
关键词：
AIDS/HIV problem Adherence Anti-HIV Agents Binding Sites Biochemical Biological Assay Child Childhood Complex Computer Models Deglutition Disease Docking Drug Design Drug Modelings Drug resistance Formulation Goals Health Homology Modeling Human Infant Lead Life Liquid substance Lopinavir Lopinavir/Ritonavir Masks Medicine Modeling Molecular Mutagenesis Organic Synthesis Outcome Patients Pharmaceutical Preparations Receptor Activation Reporting Research Research Proposals Resistance development Structural Models Structure Taste Buds Taste Perception Testing Visual base chemical synthesis cheminformatics dosage experimental study high throughput screening improved lead optimization liquid formulation molecular dynamics molecular modeling novel pediatric human immunodeficiency virus pill predictive modeling receptor release of sequestered calcium ion into cytoplasm simulation small molecule inhibitor success viral resistance virtual

项目摘要

Project Summary: The goal of this research proposal is to understand the molecular basis of blocking bitter taste for HIV/AIDS drugs so that their often unpleasant bitter taste can be eliminated. Some drugs have a strong bitter taste, which makes it a challenging task for patients to take them, especially for infants and young children. Because many children cannot swallow pills, pediatric medicines usually come in liquid or syrup form, which frequently taste bitter and is very difficult to mask, even in flavored liquid formulations. It has been reported that when children refuse to take the bitter-tasting HIV/AIDS drugs, and do not get the proper dosage of their drugs, they can develop resistance to the drugs, which has serious consequences for their health. Therefore, there is a need to develop bitter taste blockers to mask the unpleasant taste of HIV/AIDS drugs. Understanding the mechanism of bitter-tasting drug-induced TAS2R receptor activation is likely to lead to discovering bitter taste blockers, which could be used to mask the unpleasant taste of HIV/AIDS drugs. In this proposal, we have developed testable models of the HIV/AIDS drug- TAS2R receptors by computational approaches and our plan is to test them experimentally. Moreover, using structure-based drug design and organic synthesis we aim to discover novel human TAS2R specific blockers to mask the unpleasant bitter taste of different HIV/AIDS drugs.

项目概要：本研究计划的目标是了解阻断苦味的分子基础艾滋病毒/艾滋病药物，这样它们通常令人不快的苦味就可以消除。有些药物具有强烈的苦味，这使得患者服用它们是一项具有挑战性的任务，尤其是对于婴儿和幼儿。因为许多儿童无法吞咽药片、儿科药物通常以液体或糖浆形式出现，通常味道很苦并且很难掩盖，即使是调味液体配方。据报道，当孩子们拒绝接受苦味的艾滋病毒/艾滋病药物，并且没有得到适当剂量的药物，他们可能会发展对药物产生耐药性，这对他们的健康造成严重后果。因此，有一个需要开发苦味阻滞剂来掩盖艾滋病毒/艾滋病药物的难闻味道。了解苦味药物诱导 TAS2R 受体激活的机制可能导致发现苦味阻滞剂，可用于掩盖苦味艾滋病毒/艾滋病药物。在这项提案中，我们开发了艾滋病毒/艾滋病药物的可测试模型 TAS2R 受体通过计算方法，我们的计划是通过实验测试它们。此外，利用基于结构的药物设计和有机合成，我们的目标是发现新的药物人类 TAS2R 特异性阻断剂可掩盖不同 HIV/AIDS 药物的难闻苦味。