Background: The SARS-CoV-2 virus is a new highly contagious Coronavirus with a positive-sense RNA encoding 16 non-structural proteins (nsps16, nsp15, nsp3). In this study, the coronavirus pathogenicity and the losartan functional ligand for inhibiting TRPM2 and macrodomain have been molecularly evaluated.Material and method: In this study, the structures of macrodomain binding ADP ribose in CoVs and human Transient Receptor Potential Cation Channel Subfamily M Member 2 (TRPM2) protein were downloaded from protein data bank. Then, a virtual screening was done to recognize the hit compounds from GalaXi_2019-10, KnowledgeSpace_2019-05, and REALspace_2019-12 databases. This collection, then, was imported to the ligandScout software, on the base of Adenosine Diphosphate Ribose (ADPR) pharmacophore model. Result: Among seven compounds, five compounds were finally evaluated as the structural analogs of ADPR or other nucleotides, from which one compound was a non-FDA-approved sulphonamide and was removed. The other compound, losartan, was finally selected for molecular docking and molecular dynamic simulation. According to the virtual screening and docking, losartan was candidate as an effective ligand for TRPM2 and macrodomain. Conclusion: In the current study losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. The inhibitory effect of losartan on PARP has been shown and it could interfere positively in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress and apoptosis in COVID-19.
Background: Limited data exist on the clinical outcomes of patients with coronavirus disease 2019 (COVID-19) presenting with ST-segment-elevation myocardial infarction (STEMI).
Methods: This multicenter study, conducted in 6 centers in Iran, aimed to compare baseline clinical and procedural data between a case group, comprising STEMI patients with COVID-19, and a control group, comprising STEMI patients before the COVID-19 pandemic, and to determine in-hospital infarct-related artery thrombus grades and major adverse cardio-cerebrovascular events (MACCEs), defined as a composite of deaths from any cause (cardiovascular and noncardiovascular), nonfatal strokes, and stent thrombosis.
Results: No significant differences were observed between the 2 groups regarding baseline characteristics. Primary percutaneous coronary intervention (PPCI) was performed in 72.9% of the cases and 98.5% of the controls (P=0.043), and primary coronary artery bypass grafting was performed in 6.2% of the cases and 1.4% of the controls (P=0.048). Successful PPCI procedures (final TIMI flow grade III) were significantly fewer in the case group (66.5% vs 93.5%; P=0.001). The baseline thrombus grade before wire crossing was not statistically significantly different between the 2 groups. The summation of thrombus grades IV and V was 75% in the case group and 82% in the control group (P=0.432). The rate of MACCEs was 14.5% and 2.1% in the case and control groups, respectively (P=0.002).
Conclusion: In our study, the thrombus grade had no significant differences between the case and control groups; however, the in-hospital rates of the no-reflow phenomenon, periprocedural MI, mechanical complications, and MACCEs were statistically significantly higher in the case group.
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