RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may keep patients in a clinically asymptomatic state by blocking cellular innate antiviral immunity, but the molecular mechanism remains unclear. Here, we screened the viral proteins of SARS-CoV-2 and found that the spike (S) protein inhibits the activation of interferon-stimulated genes (ISGs) and even reduces the expression of these genes to below background values. Mechanistically, the S protein interacted with STAT1, STAT2, and IRF9 and impedes the phosphorylation of STAT1/STAT2, thus preventing the formation of the interferon-stimulating gene factor 3 (ISGF3) complex and inhibiting the downstream production of Interferon-stimulated genes (ISGs). Remarkably, we also have found that the inhibitory mechanism of the S protein was conservative among SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV, MERS-CoV, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Truncation studies indicated that the most conserved S2 domain played a major inhibitory role. Altogether, our findings unveil a new mechanism by which SARS-CoV-2 S protein attenuated the hosts antiviral immune response and provide new insights into the pathogenic mechanism of coronavirus.
RESUMO
Aim To investigate the effects of emodin on the contraction of gallbladder smooth muscle(GBSM)and the L-type calcium current in GBSM cells.Methods Gallbladder muscle strips were obtained from adult guinea pigs and the resting tension was recorded.Gallbladder smooth muscle cells were isolated by enzymatic digestion,and calcium current was recorded by the whole-cell patch clamp method.Results Emodin-induced contraction of GBSM was significantly attenuated by pretreatment with nifedipine.Emodin increased the L-type calcium current in a dose-dependent manner.When 10 ?mol?L-1 emodin was applied to GBSM cells,the amplitude of L-type calcium current at +10 mV was enhanced by(45.2?2.26)%.In the presence of PKC inhibitor,staurosporine,emodin did not significantly affect the calcium current.Conclusion Emodin enhances L-type calcium current via PKC-dependent pathway and promotes gallbladder contraction.
