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Top1. Introduction
Before the first clinical reports of HIV in 1981, the only knowledge of the disease was that it had a relationship with the human immune system and the bloodstream. The United States and some African countries performed intensive research on HIV since 1982, and from the results, the disease became known as AIDS (acquired immunodeficiency syndrome). In the mid-1980s in Brazil, the disease became known as the disease of the 5H: homosexuals, hemophiliacs, Haitians, heroin addicts and hookers (Goodkin et al., 2017; Goulart et al., 2018).
According to the World Health Organization (WHO), about 38 million people live with HIV worldwide, of these only 23.3 million infected received treatment by the end of 2018, accounting for 62% of the total infected. These numbers are increasingly attracting research in search of new anti-HIV drug candidates that offer a therapeutic effect with less negative impact on humans due to toxicity.
Because the life cycle of HIV is well elucidated, most research involving anti-HIV treatment assumes the need for inhibition of the 3 enzymes involved in viral multiplication: protease (PR), integrase (IN) and reverse transcriptase (RT). These are the most widely studied therapeutic targets for HIV-1 in Patel, Homaei, El-Seedi, & Akhtar, (2018).
Cheminformatics has grown over the years, and has made important contributions to pharmaceutical sciences, including the possibility to rationally design bioactive molecules for the treatment of diseases, by either the creation of new drugs or the structural modification existing drugs (Pinheiro-de-oliveira et al., 2018).
In silico methods have helped synthetic chemists, phytochemical specialists, and pharmacologists lower their input costs and time, as screening for a specific biological activity can be done using computational tools, with fewer resources than a classical laboratory experiment (Alves, 2014; Trossini, 2008).
With modern tools, it is possible to screen the candidate molecules based on molecular characteristics suitable for specific biological activity, to analyze the energies and ligand-receptor interactions at a given active site, to verify the stability and dynamic behavior of a ligand at a given receptor, and to perform chemometric analyses such as partial least squares (PLS), principal component analysis (PCA) and consensus PCA (CPCA), and theoretical pharmacophoric studies until proposing more promising biological profile structures (Cruz, 2016; Lopes & Figueiredo, 2018).
The aim of this research is the discussion of in silico studies involving 2-aminothiophenic against HIV-1, through the enzymatic inhibition of targets involved in the retroviral life cycle, and it is expected to contribute studies with retroviral activity, mainly HIV.
Top2. Materials And Methods
In this paper, a virtual hybrid screening with 180 2-aminothiophenic compounds was initially performed (https://doi.org/10.6084/m9.figshare.9722099). The compounds were synthesized in the Synthesis Laboratory and Vectorization of molecules at UEPB (Paraíba State University) whose structures were provided by Professor Dr. Francisco Jaime Mendonça Júnior. This study consists of a ligand-based approach together with a combined form of protein-based approach. Thus, it is possible to obtain molecules with better pharmacological profiles in silico by analyzing bioavailability, absorption, cytotoxicity risks, ligand-receptor interaction, active site stability and prediction of biological activity (Hansmann, Miyaji, & Dressman, 2018).