Association between renin-angiotensin system inhibitor and the risk of CMV pneumonia:a Mendelian randomization study

Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.

Mechanism Study of Aliskiren and Its Analogues by Molecular Dynamic Simulation

The further interaction mechanism towards renin inhibitors was revealed by comparison of renin with different active inhibitors in aqueous solution.Molecular docking and molecular dynamics(MD)simulations were combined for the research.The results reflected that electrostatic and hydrophobic effects were the major interactions for renin inhibitors forming complexes with renin,and some residues were the key to the formation of complex,especially Asp38/Asp226.The factor of different activities performed in renin inhibitors was illustrated as well.For the higher active renin inhibitor,it possessed stronger affinity with renin,and its detected conformation was more extended to fit for the key binding site.This promoted the capacity to form special interactions with the key residues.While conformation of the lower active renin inhibitor performed folded in the active site of renin,the interactions to the important pocket S3sp was restricted,resulting in undesirable bioactivity.