RESUMO
Objective: Despite the development of several vaccines against severe acute respiratory syndrome coronavirus-2, the need for an additional prophylactic agent is evident. In recent in silico studies, isovitexin exhibited a higher binding affinity against the human angiotensin converting-enzyme 2 (hACE2) receptor than existing antiviral drugs. The research aimed to find out the point specificity of isovitexin for the hACE2 receptor and to assess its therapeutic potential, depending on the stability of the isovitexin-hACE2 complex. Materials and Methods: The pharmacokinetic profile of isovitexin was analyzed. The crystal structure of the hACE2 receptor and the ligand isovitexin were docked to form a ligand-protein complex following molecular optimization. To determine the isovitexin-hACE2 complex stability, their binding affinity, hydrogen bonding, and hydrophobic interactions were studied. Lastly, the root mean square deviation (RMSD), root mean square fluctuation, solvent accessible surface area, molecular surface area, radius of gyration (Rg), polar surface area, and principal component analysis values were found by simulating the complex with molecular dynamic (MD). Results: The predicted Lethal dose50 for isovitexin was 2.56 mol/kg, with an acceptable maximum tolerated dose and no hepatotoxicity or AMES toxicity. Interactions with the amino acid residues Thr371, Asp367, Glu406, Pro346, His345, Phe274, Tyr515, Glu375, Thr347, Glu402, and His374 of the hACE2 protein were required for the high binding affinity and specificity of isovitexin. Based on what was learned from the MD simulation, the hACE2 receptor-blocking properties of isovitexin were looked at. Conclusions: Isovitexin is a phytochemical with a reasonable bioactivity and safety profile for use in humans, and it can potentially be used as a hACE2-specific therapeutic to inhibit COVID-19 infection.
RESUMO
Acute coronary syndrome (ACS) comprises a pathophysiological spectrum of cardiovascular diseases related to atherosclerotic coronary plaque erosion. Oxidative stress and inflammation play pivotal roles in the development and progression of atherosclerosis, which affects circulatory proteins, including albumin and fibrinogen, thereby causing an imbalance in albumin to globulin and fibrinogen to albumin ratios. This study aimed to assess the effect of oxidative stress on circulatory proteins, correlate these parameters, and investigate their significance in patients with ACS. In this case-control study, the major blood proteins in patients with ACS and a control group were evaluated using standard methods. Out of 70 ACS cases, 75.7% had ST-elevation myocardial infarction (STEMI), 18.6% had non-STEMI, and 5.7% had unstable angina. The mean cardiac troponin I level in patients was 12.42 ng/mL. The patients demonstrated a significantly reduced level of human serum albumin (HSA), 3.81 ± 0.99 g/dL, compared to controls, 5.33 ± 0.66 g/dL. The albumin to globulin ratio (AGR) was significantly depressed in patients while their mean fibrinogen level and the fibrinogen to albumin ratio (FAR) were significantly higher. Multivariate logistic regression analysis showed that albumin and fibrinogen were significantly associated with the risk of ACS, showing the potential of these parameters to be used for risk assessment of ACS. The ischemia modified albumin (IMA) and protein carbonyls were significantly higher in patients which showed significant positive correlations with FAR. Albumin, IMA and protein carbonyls were found to have high diagnostic sensitivity and specificity for ACS. Overall, these circulatory and modified proteins in ACS patients, particularly lower HSA, AGR, and higher IMA and protein carbonyls may help assess risk.
