Alberto Anael Viana Pinto, da Silva Ferreira Natiele Carla, Soares Rafael Ferreira, Alves Luiz Anastacio
Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Front Pharmacol. 2020 Sep 29;11:01221. doi: 10.3389/fphar.2020.01221. eCollection 2020.
P2 receptors are a family of transmembrane receptors activated by nucleotides and nucleosides. Two classes have been described in mammals, P2X and P2Y, which are implicated in various diseases. Currently, only P2Y12 has medicines approved for clinical use as antiplatelet agents and natural products have emerged as a source of new drugs with action on P2 receptors due to the diversity of chemical structures. In drug discovery, virtual screening (VS) techniques have become popular because they have numerous advantages, which include the evaluation of thousands of molecules against a target, usually proteins, faster and cheaper than classical high throughput screening (HTS). The number of studies using VS techniques has been growing in recent years and has led to the discovery of new molecules of natural origin with action on different P2X and P2Y receptors. Using different algorithms it is possible to obtain information on absorption, distribution, metabolism, toxicity, as well as predictions on biological activity and the lead-likeness of the selected hits. Selected biomolecules may then be tested by molecular dynamics and, if necessary, rationally designed or modified to improve their interaction for the target. The algorithms of these tools are being improved to permit the precision development of new drugs and, in the future, this process will take the front of drug development against some central nervous system (CNS) disorders. Therefore, this review discusses the methodologies of tools concerning P2 receptors, as well as future perspectives and discoveries, such as the employment of artificial intelligence in drug discovery.
P2受体是一类由核苷酸和核苷激活的跨膜受体。在哺乳动物中已描述了两类，即P2X和P2Y，它们与多种疾病有关。目前，只有P2Y12有被批准用于临床的抗血小板药物，由于化学结构的多样性，天然产物已成为作用于P2受体的新药来源。在药物研发中，虚拟筛选（VS）技术因其具有诸多优势而变得流行，这些优势包括针对一个靶点（通常是蛋白质）评估数千种分子，比传统的高通量筛选（HTS）更快、更便宜。近年来，使用VS技术的研究数量一直在增加，并导致发现了作用于不同P2X和P2Y受体的天然来源新分子。使用不同的算法可以获得有关吸收、分布、代谢、毒性的信息，以及对生物活性和所选命中物类药性质的预测。然后可以通过分子动力学对所选生物分子进行测试，如有必要，进行合理设计或修饰以改善它们与靶点的相互作用。这些工具的算法正在不断改进，以实现新药的精准研发，未来，这一过程将在针对某些中枢神经系统（CNS）疾病的药物研发中占据主导地位。因此，本综述讨论了有关P2受体的工具方法，以及未来的前景和发现，例如人工智能在药物研发中的应用。
