Towards the de novo Design of HIV-1 Protease Inhibitors based on Natural Products

In the world, the acquired immunodeficiency syndrome (AIDS) caused by the human immunode-ficiency 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 only a way to control HIV, not a cure as such, so effective treatment must be developed to control AIDS. However, de-veloping a drug is not an easy task. The enormous amount of work and financial invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help to generate and identify novel molecules. Using the de novo design, new novel molecules can be de-veloped from scratch 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, a large number of sp3 atoms, and chiral centers; and the pseudo-natural product is a combination of natural products fragments that conserve the desired structural characteristics from different natural products.