RESUMEN
The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 µM and 400 µM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.
Asunto(s)
Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Donantes de Óxido Nítrico/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , SARS-CoV-2/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Dominio Catalítico/efectos de los fármacos , Chlorocebus aethiops , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Humanos , Modelos Moleculares , Óxido Nítrico/farmacología , SARS-CoV-2/enzimología , SARS-CoV-2/fisiología , Células Vero , Inhibidores de Proteasa Viral/farmacologíaRESUMEN
Objective To evaluate the clinical efficacy of acupoint injection with BCG-polysaccharide nucleic acid (BCG-PSN) in treating bronchial asthma. Method Seventy-two patients with bronchial asthma were randomized into an acupoint injection group and a muscular injection group, 36 cases in each group. The acupoint injection group was intervened by acupoint injection with BCG-PSN to Zusanli (ST36) and Dingchuan (EX-B1) alternately, 1 mL for two points in total each time; the muscular injection group was intervened by muscular injection at the same dose and frequency, twice a week, for successive 3 months. The pulmonary function and asthma control test (ACT) were estimated before and after intervention and during March of the next year. Result After intervention, the FEV1 values were (80.97±2.31)% and (80.78±2.56)% respectively in the acupoint injection group and muscular injection group, and PEF values were (6.50±0.21)L/s and (6.48±0.25)L/s, and the between-group differences were statistically insignificant (P>0.05). The ACT score was (23.02±1.03) in the acupoint injection group, significantly better than (22.40±2.04) in the muscular injection group (P<0.05). The follow-up study showed that the ACT score in the acupoint injection group was superior to that in the muscular injection group (P<0.05). Conclusion Acupoint injection and muscular injection with BCG-PSN can equally improve the pulmonary function in bronchial asthma, while the acupoint injection can produce a more significant effect than muscular injection in improving ACT.