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

Abstract

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.

Quantitative structure–activity relationship-based computational approaches

“…After broad in vitro and in vivo considers, these in-house VS hits might arise as helpful alternatives for COVID-19. This investigation may likewise propel restorative physicists to plan comparative kinds of mixtures in desires to trigger natural power just as viability without gathering poison levels ( Płonka et al, 2020 , Tejera et al, 2020 ).…”

Synthesis, characterized, QSAR studies and molecular docking of some phosphonates as COVID-19 inhibitors

“…Quantitative Structure-Activity relationship (QSAR) is a tool to discover the relationship between the structure and activity of chemical compounds. In the face of unknown disease particularly COVID-19, this technique and molecular docking have brought benefits to design and produce new drugs [ [18] , [19] , [20] , [21] ].…”

Synthesis, Spectral Characteristics, and Molecular Docking Studies of 2,4-Dichloro-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide

“…These compounds are of particular interest as biologically active compounds [2]. Among the derivatives of 1,3,4-thiadiazole are substances with antitumor [3][4][5][6][7][8][9][10][11], antiviral [11][12][13][14][15][16][17], antimicrobial [10,[18][19][20][21][22][23][24][25][26][27][28][29][30], antioxidant [29,30], neuroprotective [31], antiprotozoal [32], and anti-inflammatory [33,34] activity. In addition, these substances act as inhibitors of acetylcholinesterase [35,36], αglucosidase [37], and carbonic anhydrase [38].…”