Docking and QSAR of Aminothioureas at the SARS-CoV-2 S-Protein–Human ACE2 Receptor Interface

Molecules

Wojciech Płonka¹  Agata Paneth²  Piotr Paneth³ 

[1] Center for Bioinformatics (ZBH), Universität Hamburg, 20146 Hamburg, Germany;Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, Chodźki 4a, 20-093 Lublin, Poland;Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, Żeromskiego 116, 90-924 Lodz, Poland;

关键词: SARS-CoV-2;    aminothioureas;    docking;    QSAR;    ADMET;   

DOI  :  10.3390/molecules25204645

来源: DOAJ

【 摘 要 】

Docking of over 160 aminothiourea derivatives at the SARS-CoV-2 S-protein–human
ACE2 receptor interface, whose structure became available recently, has been evaluated for its
complex stabilizing potency and subsequently subjected to quantitative structure–activity
relationship (QSAR) analysis. The structural variety of the studied compounds, that include 3
different forms of the N–N–C(S)–N skeleton and combinations of 13 different substituents alongside
the extensive length of the interface, resulted in the failure of the QSAR analysis, since different
molecules were binding to different parts of the interface. Subsequently, absorption, distribution,
metabolism, and excretion (ADME) analysis on all studied compounds, followed by a toxicity
analysis using statistical models for selected compounds, was carried out to evaluate their potential
use as lead compounds for drug design. Combined, these studies highlighted two molecules among
the studied compounds, i.e., 5-(pyrrol-2-yl)-2-(2-methoxyphenylamino)-1,3,4-thiadiazole and 1-
(cyclopentanoyl)-4-(3-iodophenyl)-thiosemicarbazide, as the best candidates for the development
of future drugs.

【 授权许可】

Unknown