Structural Insights into the Protective Mechanisms against O2 in the [NiFe]-Hydrogenases

Author(s):  
Yasuhito Shomura
Author(s):  
E.I. Sidorenko ◽  

The lecture provides a detailed description of the development of retinal vessels, vasculogenesis and angiogenesis. The cascade of protective mechanisms of the organism of the system of combating hyperoxia, the system of combating circulatory hypoxia and the key growth factors of the vascular endothelium during angiogenesis are shown. The pathogenesis of retinopathy of prematurity is described and the first phase of ROP development is analyzed in detail, the reasons for the delay in the maturation of vascular autoregulation are explained. The author proposed to distinguish the first preclinical phase in the ROP classification. In contrast to the modern concentration of attention of ophthalmologists on the active and cicatricial stages, the author proposes to pay special attention to the study of the preclinical stage of ROP, where its pathogenesis is formed.


Author(s):  
Parth Sarthi Sen Gupta ◽  
Satyaranjan Biswal ◽  
Saroj Kumar Panda ◽  
Abhik Kumar Ray ◽  
Malay Kumar Rana

<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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