Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling.

Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) became pandemic by the end of March 2020. In contrast to the 2002–2003 SARS-CoV outbreak, which had a higher pathogenicity and lead to higher mortality rates, SARSCoV-2 infection appears to be much more contagious. Moreover, many SARS-CoV-2 infected patients are reported to develop low-titer neutralizing antibody and usually suffer prolonged illness, suggesting a more effective SARS-CoV-2 immune surveillance evasion than SARS-CoV. This paper summarizes the current state of art about the differences and similarities between the pathogenesis of the two coronaviruses, focusing on receptor binding domain, host cell entry and protease activation. Such differences may provide insight into possible intervention strategies to fight the pandemic.

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In the presence of micromolar concentrations of Ca2+, both protein kinase C and a cytosolic Ca2+-requiring neutral proteinase of human neutrophils become associated with the neutrophil membrane. Binding to the membrane results in activation of the proteinase, which then catalyzes limited proteolysis of the kinase to produce a form that is fully active in the absence of Ca2' and phospholipid. This irreversibly activated protein kinase is released from the membrane and may thus have access, in the intact cell, to intracellular protein substrates. In the absence of the proteinase, Ca2+ promotes the binding of protein kinase C, but conversion to the Ca2+/phospholipid-independent form does not occur and the kinase remains associated with the membrane fraction.Protein kinase C was originally described in rat brain as a soluble, cAMP-independent proenzyme (1) that was converted to the active kinase by the action of a cytosolic Ca2+-requiring proteinase (2, 3). The native "proenzyme" was later shown to require Ca2' and phospholipid (4,5) and to be further activated by diacylglycerol (6), which markedly increased its affinity for both Ca2' and phospholipid (for reviews, see refs. 7 and 8). Activation of protein kinase C in stimulated platelets has been attributed to the formation of diacylglycerol generated by phospholipase C from inositol phospholipids (7,9). An irreversible activation by limited proteolysis has also been described in platelets treated with phospholipase C (10) or phorbol 12-myristate 13-acetate (11) Isolation of Neutrophils. This was based on the procedure of Boyum (14). Freshly collected, heparinized human blood (100 ml) from healthy donors was treated with 1.6% (wt/vol) dextran (final concentration) and left at 25-28°C for -1 hr. The sedimented erythrocytes were removed and the supernatant solution (40 ml) was collected and layered onto 10 ml of 6% Ficoll 400 solution containing 0.17% (vol/vol) Urovison. The gradient was centrifuged at 800 x g for 20 min and the pellet obtained was resuspended in 10 ml of 0.2% NaCl to lyse the contaminating red cells. After 30 sec, 10 ml of 1.6% NaCl was added; the cells were recovered by centrifugation at 400 x g for 5 min and washed three times with 0.01 M sodium phosphate, pH 7.4/5 mM KCl/0.12 M NaCl/24 mM NaHCO3/5 mM glucose. Prior to use, the cells were maintained in an ice bath in the same medium at a concentration of 15-20 x 106 cells per ml. The cell population obtained consisted of 96% neutrophils, as evaluated by microscopic examination. The remaining 4% consisted of 3.5% eosinophils and 0.4% monocytes.Isolation of Human Platelets. Fresh human blood platelet concentrates were obtained from a blood bank and washed platelets were prepared as described by Baenziger and Majerus (15). The platelets were washed and suspended at a final concentration of 1010 cells per ml in the same buffer employed for the neutrophils.Isolation of the Soluble and Particulate Fractions from Neutrophils and Platelets. These were prepared from lysates obtained by sonicating ...