RESUMO
SARS-CoV-2 currently lacks effective first-line drug treatment. We present promising data from in silico docking studies of new Methisazone compounds (modified with calcium, Ca; iron, Fe; magnesium, Mg; manganese, Mn; or zinc, Zn) designed to bind more strongly to key proteins involved in replication of SARS-CoV-2. In this in silico molecular docking study, we investigated the inhibiting role of Methisazone and the modified drugs against SARS-CoV-2 proteins: ribonucleic acid (RNA)-dependent RNA polymerase (RdRp), spike protein, papain-like protease (PlPr), and main protease (MPro). We found that the highest binding interactions were found with the spike protein (6VYB), with the highest overall binding being observed with Mn-bound Methisazone at -8.3 kcal/mol, followed by Zn and Ca at -8.0 kcal/mol, and Fe and Mg at -7.9 kcal/mol. We also found that the metal-modified Methisazone had higher affinity for PlPr and MPro. In addition, we identified multiple binding pockets that could be singly or multiply occupied on all proteins tested. The best binding energy was with Mn-Methisazone versus spike protein, and the largest cumulative increases in binding energies were found with PlPr. We suggest that further studies are warranted to identify whether these compounds may be effective for treatment and/or prophylaxis.
Assuntos
Antivirais/química , Metais/química , Metisazona/química , Simulação de Acoplamento Molecular , SARS-CoV-2/química , Antivirais/metabolismo , Cálcio/química , Cálcio/metabolismo , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , RNA-Polimerase RNA-Dependente de Coronavírus/química , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Desenho de Fármacos , Humanos , Ferro/química , Ferro/metabolismo , Magnésio/química , Magnésio/metabolismo , Manganês/química , Manganês/metabolismo , Metais/metabolismo , Metisazona/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Zinco/química , Zinco/metabolismo , Tratamento Farmacológico da COVID-19RESUMO
OBJECTIVE: To compare the three common methods of endotracheal tube cuff inflation (sealing pressure, precise standard pressure or finger estimation) regarding the effective tracheal seal and the incidence of post-intubation airway complications. METHODS: Seventy-five adult patients scheduled for N(2) O free general anesthesia were enrolled in this study. After induction of anesthesia, endotracheal tubes size 7.5 mm for female and 8.0 mm for male were used. Patients were randomly assigned into one of three groups. Control group (n=25), the cuff was inflated to a pressure of 25 cm H(2)O; sealing group (n=25), the cuff was inflated to prevent air leaks at airway pressure of 20 cm H(2)O and finger group (n=25), the cuff was inflated using finger estimation. Tracheal leaks, incidence of sore throat, hoarseness and dysphagia were tested. RESULTS: Although cuff pressure was significantly low in the sealing group compared to the control group (P<0.001), the incidence of sore throat was similar in both groups. On the other hand, cuff pressure as well as the incidence of sore throat were significantly higher in the finger group compared to both the control and the sealing group (P<0.001 and P=0.008). The incidence of dysphagia and hoarseness were similar in the three groups. None of the patients in the three groups developed air leak around the endotracheal tube cuff.. CONCLUSIONS: In N(2)O, free anesthesia sealing cuff pressure is an easy, undemanding and safe alternative to the standard technique, regarding effective sealing and low incidence of sore throat.