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The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to more than 270 million infections and 5.3 million of deaths worldwide. Several major variants of SARS-CoV-2 have emerged and posed challenges in controlling the pandemic. The recently occurred Omicron variant raised serious concerns about reducing the efficacy of vaccines and neutralization antibodies due to its vast mutations. We have modelled the complex structure of the human ACE2 protein and the receptor binding domain (RBD) of Omicron Spike protein (S-protein), and conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron RBD binds more strongly to the human ACE2 protein than the original strain. The mutations at the ACE2-RBD interface enhance the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causing agent of the COVID-19 pandemic, has spread globally. Angiotensin-converting enzyme 2 (ACE2) has been identified as the host cell receptor that binds to receptor-binding domain (RBD) of the SARS-COV-2 spike protein and mediates cell entry. Because the ACE2 proteins are widely available in mammals, it is important to investigate the interactions between the RBD and the ACE2 of other mammals. Here we analyzed the sequences of ACE2 proteins from 16 mammals and predicted the structures of ACE2-RBD complexes. Analyses on sequence, structure, and dynamics synergistically provide valuable insights into the interactions between ACE2 and RBD. The comparison results suggest that the ACE2 of bovine, cat and panda form strong binding with RBD, while in the cases of rat, least horseshoe bat, horse, pig, mouse and civet, the ACE2 proteins interact weakly with RBD.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix 1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.
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A novel coronavirus (the SARS-CoV-2) has been identified in January 2020 as the causal pathogen for COVID-19 pneumonia, an outbreak started near the end of 2019 in Wuhan, China. The SARS-CoV-2 was found to be closely related to the SARS-CoV, based on the genomic analysis. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2 as well, initiated by the binding of the spike protein to the human ACE2. Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The predicted model is highly consistent with the experimentally determined complex structures. Plausible binding modes between human ACE2 and the RBD were revealed from all-atom MD simulations. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. Two mutants mimicking rat ACE2 were modeled to study the mutation effects on RBD binding to ACE2. The simulations showed that the N-terminal helix and the K353 of the human ACE2 alter the binding modes of the CoV2-RBD to the ACE2.
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Objective To compare the short term clinical efficacy of percutaneous resection and laparoscopic deroofing of renal cysts.Methods From October 2013 to June 2016,the data from 39 cases with renal cysts were followed for approximately 22 months (ranging 5-36 months).Patients were randomized into two groups.In the resectoscopic group(17 pts),the mean age of those patients was 57 years (ranging 34-81 years).The mean size of these cysts was 6.4cm (ranging 5.4-8.2 cm).The mean preoperative creatinine was 66.5μmol/L (ranging 38.1-108.8μ mol/L).The mean preoperative sodium was 141.4μ mol/L(ranging 135.6-145.1μmol/L).The mean preoperative potassium was 4.0μmol/L (ranging 3.4-4.7 μmol/L).In the latter laparoscope (22pts),the mean age of these patients was 60 years (ranging 46-73 years).The mean size of these cysts was 6.8cm (ranging 4.3-8.9cm).The mean preoperative creatinine was 74.8μmol/L (ranging 48.6-141.9μmol/L).The mean preoperative sodium was 141.5μmol/L(ranging 135.0-146.1 μmol/L).The mean preoperative potassium was 4.0μmol/L (ranging 3.1-4.8μmol/L).The operative time,blood loss,days of drainage,hospital stay and complications were compared with the two groups.Results All of the 39 cases were accepted the procedure successfully without open conversion.Compared the resectoscopic group with Laparoscopic,the mean operative time was 29.7 min (ranging 15-50 min) and 63.0min (ranging 20-1 00 min),mean blood loss was 36.6ml(ranging 10-80 ml) and 60.4ml(ranging 10-200 ml),days of drainage was 2.3 days and 3.1 days,hospital stay was 3.7 days and 5.1 days,the mean postoperative creatinine was 67.4 μmol/L(ranging 43.8-95.5 μmol/L) and 68.9μmol/L(ranging 46.5-157.6 μmol/L),the mean postoperative sodium was 141.2μmol/L(ranging 136.0-147.2 μmol/L) and 141.6 μmol/L(ranging 136.0-147.2 μmol/L),the mean postoperative potassium was 3.8 μmol/L (ranging 3.2-4.3 μmol/L) and 3.8μmol/L (ranging 3.3-4.3 μmol/L).The overall postoperative pathology was renal cysts.All cases were followed for approximately 19 months (ranging 6-35 months) and 22 months (ranging 5-36 months) in reseetoscopic and laparoscopic group respectively.No cysts recurrence was found by ultrasound.Conclusions Compared with laparoscopic deroofing,use of resectoscopic technology significantly enhances the possibility of achieving better intraoperative results in all patients with renal cysts.Percutaneous resection of simple renal cysts is safe and feasible.
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To develop a method for the distinction of genuine Gastrodia elata B1. from its four falsified plants of common occurrence and determination of its active principle, gastrodin by capillary electrophoresis. Methods The electrophoretic conditions were a buffer solution containing 24 mmol/L borate (pH=9.4), at a voltage of 16 kV. Results The electrophorograms obtained under the above conditions showed easily distinguishable differences. Baseline separation of gastrodin was achieved and its quantitative analysis can be accomplished within 15 min. The linear correlation equation was Y=-0.048+7.79X (r=0.999). Conclusion This method could serve as an easy and precise method for the quality control of G. elata.
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Object To develop a method for the distinction of genuine Gastrodia elata B1 from its four falsified plants of common occurrence and determination of its active principle, gastrodin by capillary electrophoresis Methods The electrophoretic conditions were a buffer solution containing 24 mmol/L borate (pH=9 4), at a voltage of 16 kV Results The electrophorograms obtained under the above conditions showed easily distinguishable differences Baseline separation of gastrodin was achieved and its quantitative analysis can be accomplished within 15 min The linear correlation equation was Y=-0 048+7 79X (r=0 999) Conclusion This method could serve as an easy and precise method for the quality control of G elata