DIFACQUIM Research Group, Department of Pharmacy, School of Chemistry, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico.
Biomolecules. 2021 Dec 1;11(12):1805. doi: 10.3390/biom11121805.
Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 million people were infected. Antiretrovirals are a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available in the supplementary material.
获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）引起的，它仍然是一个公共卫生问题。2020 年，有 68 万人死于与 HIV 相关的原因，有 150 万人感染。抗逆转录病毒药物是控制 HIV 感染的一种方法，但不能治愈艾滋病。因此，必须开发有效的治疗方法来控制艾滋病。开发一种药物并非易事，需要投入大量的工作和经济资源。出于这个原因，采用计算机辅助药物设计方法非常方便，它可以帮助生成和识别新的分子。使用从头设计，可以使用片段作为构建块来开发新的分子。在这项工作中，我们从天然产物片段开发了一个 HIV-1 病毒蛋白酶抑制剂的虚拟聚焦化合物库。天然产物的特点是具有大量的功能基团、许多 sp 原子和手性中心。伪天然产物是将不同天然产物的所需结构特征组合在一起的天然产物片段。天然产物片段的 HIV-1 病毒蛋白酶抑制剂虚拟化合物的化学空间可视化的交互式版本可在补充材料中免费获得。
