scholarly journals Structural insights into the mechanism of the membrane integral N-acyltransferase step in bacterial lipoprotein synthesis

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Maciej Wiktor ◽  
Dietmar Weichert ◽  
Nicole Howe ◽  
Chia-Ying Huang ◽  
Vincent Olieric ◽  
...  
Keyword(s):  
Lipoprotein Synthesis ◽  
Structural Insights ◽  
Bacterial Lipoprotein

scholarly journals Structural insights into bacterial lipoprotein biosynthesis

2017 ◽  
Vol 73 (a1) ◽  
pp. a116-a116
Author(s):  
Cameron L. Noland ◽  
Michele Kattke ◽  
Susan Gloor ◽  
Jingyu Diao ◽  
Homer Pantua ◽  
...  
Keyword(s):  
Structural Insights ◽  
Bacterial Lipoprotein

Binding Mechanism and Structural Insights into the Identified Protein Target of Covid-19 with In-Vitro Effective Drug Ivermectin

2020 ◽  
Author(s):  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Saroj Kumar Panda ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana
Keyword(s):  
Ternary Complex ◽  
Bound State ◽  
Molecular Target ◽  
Cooperative Interaction ◽  
Effective Drug ◽  
Rna Dependent Rna Polymerase ◽  
Protein Target ◽  
Ternary Complex Formation ◽  
Structural Insights

<p>While an FDA approved drug Ivermectin was reported to dramatically reduce the cell line of SARS-CoV-2 by ~5000 folds within 48 hours, the precise mechanism of action and the COVID-19 molecular target involved in interaction with this in-vitro effective drug are unknown yet. Among 12 different COVID-19 targets studied here, the RNA dependent RNA polymerase (RdRp) with RNA and Helicase NCB site show the strongest affinity to Ivermectin amounting -10.4 kcal/mol and -9.6 kcal/mol, respectively. Molecular dynamics of corresponding protein-drug complexes reveals that the drug bound state of RdRp with RNA has better structural stability than the Helicase NCB site, with MM/PBSA free energy of -135.2 kJ/mol, almost twice that of Helicase (-76.6 kJ/mol). The selectivity of Ivermectin to RdRp is triggered by a cooperative interaction of RNA-RdRp by ternary complex formation. Identification of the target and its interaction profile with Ivermectin can lead to more powerful drug designs for COVID-19 and experimental exploration. </p>

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