SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells.

It is urgent to understand the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the prevention and treatment of COVID-19. The infection of SARS-CoV-2 starts when the receptor-binding domain (RBD) of viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) of the host cell, but the endocytosis details after this binding are not clear. Here, RBD and ACE2 were genetically coded and labeled with organic dyes to track RBD endocytosis in living cells. The photostable dyes enable long-term structured illumination microscopy (SIM) imaging and to quantify RBD-ACE2 binding (RAB) by the intensity ratio of RBD/ACE2 fluorescence. We resolved RAB endocytosis in living cells, including RBD-ACE2 recognition, cofactor-regulated membrane internalization, RAB-bearing vesicle formation and transport, RAB degradation, and downregulation of ACE2. The RAB was found to activate the RBD internalization. After vesicles were transported and matured within cells, RAB was finally degraded after being taken up by lysosomes. This strategy is a promising tool to understand the infection mechanism of SARS-CoV-2.

Toward Urease-free Wearable Artificial Kidney: Widened Interlayer Spacing MoS2 Nanosheets with Highly Effective Adsorption for Uremic Toxins

The high incidence of kidney disease caused by various factors (such as COVID-19) has triggered an extreme desire for wearable artificial kidney (WAK). Nevertheless, the dialysate regeneration system in WAK presents a very low adsorption capacity of urea, and must rely on the help of urease and zirconium compounds, which make the device too complex and costly, thus limiting their application. In this study, we employ the adsorption activity of defect-rich MoS2 nanosheets with widened interlayer spacing (WDR-MoS2) for the elimination of three crucial uremic toxins (urea, creatinine, and uric acid). The high adsorption performances of WDR-MoS2 are owing to the presence of abundant S atoms between the two MoS2 sheets that can efficiently adsorb uremic toxins through the unique S-N bond. Furthermore, widening the layer spacing of MoS2 is similar to adjusting the aperture of a filter, which can not only speed up the transport of uremic toxins but also prevent the passage of large molecules (such as proteins). Thus, the WDR-MoS2 can neither affect cell viability nor produce hemolysis and coagulation in the blood. Finally, a home-made WDR-MoS2 fixed-bed system without urease and zirconium compounds is used to efficiently remove uremic toxins in the dialysate. WDR-MoS2 is expected to fundamentally solve the materials science challenges in WAK and provide a new design idea for the development of high-performance 2D material-based adsorbents.