Towards the De Novo Design of HIV-1 Protease Inhibitors Based on Natural Products

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2021-12, Vol.11 (12), p.1805
• Main Authors: Chávez-Hernández, Ana L, Juárez-Mercado, K Eurídice, Saldívar-González, Fernanda I, Medina-Franco, José L
• Format: Article
• Language: English
• Subjects: Acids; Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - virology; AIDS; Antiviral agents; Artificial intelligence; Binding sites; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Carbon; Chemical compounds; Chemical elements; Chemical reactions; Clinical trials; Computers; Databases, Pharmaceutical; de novo design; Drug Design; Drug development; Drugs; FDA approval; fragment-based drug discovery; HIV; HIV Protease Inhibitors - chemical synthesis; HIV Protease Inhibitors - chemistry; HIV Protease Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - enzymology; HIV-1 inhibitors; Human immunodeficiency virus; Humans; Hydrogen bonds; Immune system; Molecular Structure; Natural products; Nitrogen; Programming languages; Proteinase inhibitors; pseudo natural products; Public health; Severe acute respiratory syndrome coronavirus 2; Structure-Activity Relationship
• ISSN: 2218-273X; 2218-273X
• 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.