论文标题
抗病毒药物通透性：病毒包膜和细胞细胞器
Antiviral Drug-Membrane Permeability: the Viral Envelope and Cellular Organelles
论文作者
论文摘要
要缩短找到有效新药所需的时间，例如抗病毒药，要考虑的关键参数是膜的渗透性，因为旨在用于渗透率较差的细胞内靶标的化合物将具有较低的疗效。在这里，我们提出了一个计算模型，该模型考虑了药物特性和膜特性，以快速评估通过冠状病毒包膜和各种细胞膜来快速评估药物的渗透性。我们分析了79种被认为是治疗SARS-COV-2的潜在候选药物，并确定它们在通过病毒诱饵和哺乳动物过程分组的不同细胞器膜中的渗透时间。计算结果与文献中存在的有关药物的生物利用度中存在的实验数据相关，显示了快速渗透与最有前途的药物之间的负相关性。该模型代表了一个重要的工具，能够评估渗透率如何影响化合物以准确而快速的方式达到预期和意外的细胞内靶标的能力。该方法是一般且灵活的，可以用于从小药物到纳米颗粒到各种生物膜的各种分子。
To shorten the time required to find effective new drugs, like antivirals, a key parameter to consider is membrane permeability, as a compound intended for an intracellular target with poor permeability will have low efficacy. Here, we present a computational model that considers both drug characteristics and membrane properties for the rapid assessment of drugs permeability through the coronavirus envelope and various cellular membranes. We analyze 79 drugs that are considered as potential candidates for the treatment of SARS-CoV-2 and determine their time of permeation in different organelle membranes grouped by viral baits and mammalian processes. The computational results are correlated with experimental data, present in the literature, on bioavailability of the drugs, showing a negative correlation between fast permeation and most promising drugs. This model represents an important tool capable of evaluating how permeability affects the ability of compounds to reach both intended and unintended intracellular targets in an accurate and rapid way. The method is general and flexible and can be employed for a variety of molecules, from small drugs to nanoparticles, as well to a variety of biological membranes.
