ABSTRACT
The present study uses molecular docking and dynamic simulations to evaluate the inhibitory effect of flavonoid glycosides-based compounds on coronavirus Main protease (Mpro) and RNA polymerase. The Molegro Virtual Docker (MVD) software is utilized to simulate and calculate the binding parameters of compounds with coronavirus. The docking results show that the selected herbal compounds are more effective than those of chemical compounds. It is also revealed that five herbal ligands and two chemical ligands have the best docking scores. Furthermore, a Molecular Dynamics (MD) simulation was conducted for Hesperidin, confirming docking results. Analysis based on different parameters such as Root-mean-square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg), Solvent accessibility surface area (SASA), and the total number of hydrogen bonds suggests that Hesperidin formed a stable complex with Mpro. Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) analysis was performed to compare Hesperidin and Grazoprevir as potential antiviral medicines, evaluating both herbal and chemical ligand results. According to the study, herbal compounds could be effective on coronavirus and are admissible candidates for developing potential operative anti-viral medicines. Hesperidin was found to be the most acceptable interaction. Grazoprevir is an encouraging candidate for drug development and clinical trials, with the potential to become a highly effective Mpro inhibitor. Compared to RNA polymerase, Mpro showed a greater affinity for bonding with Hesperidin. van der Waals and electrostatic energies dominated, creating a stable Hesperidin-Mpro and Hesperidin-RNA polymerase complex.
ABSTRACT
BACKGROUND: The effect of COVID-19 infection on post-operative mortality and the optimal timing to perform ambulatory surgery from diagnosis date remains unclear in this population. Our study was to determine whether a history of COVID-19 diagnosis leads to a higher risk of all-cause mortality following ambulatory surgery. METHODS: This cohort constitutes retrospective data obtained from the Optum dataset containing 44,976 US adults who were tested for COVID-19 up to 6 months before surgery and underwent ambulatory surgery between March 2020 to March 2021. The primary outcome was the risk of all-cause mortality between the COVID-19 positive and negative patients grouped according to the time interval from COVID-19 testing to ambulatory surgery, called the Testing to Surgery Interval Mortality (TSIM) of up to 6 months. Secondary outcome included determining all-cause mortality (TSIM) in time intervals of 0-15 days, 16-30 days, 31-45 days, and 46-180 days in COVID-19 positive and negative patients. RESULTS: 44,934 patients (4297 COVID-19 positive, 40,637 COVID-19 negative) were included in our analysis. COVID-19 positive patients undergoing ambulatory surgery had higher risk of all-cause mortality compared to COVID-19 negative patients (OR = 2.51, p < 0.001). The increased risk of mortality in COVID-19 positive patients remained high amongst patients who had surgery 0-45 days from date of COVID-19 testing. In addition, COVID-19 positive patients who underwent colonoscopy (OR = 0.21, p = 0.01) and plastic and orthopedic surgery (OR = 0.27, p = 0.01) had lower mortality than those underwent other surgeries. CONCLUSIONS: A COVID-19 positive diagnosis is associated with significantly higher risk of all-cause mortality following ambulatory surgery. This mortality risk is greatest in patients that undergo ambulatory surgery within 45 days of testing positive for COVID-19. Postponing elective ambulatory surgeries in patients that test positive for COVID-19 infection within 45 days of surgery date should be considered, although prospective studies are needed to assess this.