ABSTRACT
Emerging COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a great threat to human health and economics. Although SARS-CoV-2 entry mechanism has been explored, little is known about how SARS-CoV-2 regulates the host cell remodeling to facilitate virus invasion process. Here we unveil that SARS-CoV-2 boosts and repurposes filopodia for entry to the target cells. Using SARS-CoV-2 virus-like particle (VLP), real-time live-cell imaging and simulation of active gel model, we reveal that VLP-induced Cdc42 activation leads to the formation of filopodia, which reinforce the viral entry to host cells. By single-particle tracking and sparse deconvolution algorithm, we uncover that VLP particles utilize filopodia to reach the entry site in two patterns, surfing and grabbing, which are more efficient and faster than entry via flat plasma membrane regions. Furthermore, the entry process via filopodia is dependent on the actin cytoskeleton and actin-associated proteins fascin, formin, and Arp2/3. Importantly, either inhibition the actin cross-linking protein fascin or the active level of Cdc42 could significantly hinders both the VLP and the authentic SARS-CoV-2 entry. Together, our results highlight that the spatial-temporal regulation of the actin cytoskeleton by SARS-CoV-2 infection makes filopodia as a highway for virus entry, which emerges as an antiviral target. Significance StatementRevealing the mechanism of SARS-CoV-2 invasion is of great significance to explain its high pathogenic and rapid transmission in the world. We discovered a previously unknown route of SARS-CoV-2 entry. SARS-CoV-2 virus-like particles boost cellular filopodia formation by activating Cdc42. Using state-of-art-technology, we spatial-temporally described how virus utilize filopodia to enter the target cell in two modes: surfing and grabbing. Filopodia can directly transport the virus to endocytic hot spots to avoid the virus from disorderly searching on the plasma membrane. Our study complements current knowledge of SARS-CoV-2 that filopodia and its components not only play an important role in virus release and cell-cell transmission, but also in the entry process, and provides several potential therapeutic targets for SARS-CoV-2. HighlightsO_LISARS-CoV-2 VLP infection promotes filopodia formation by activating Cdc42 C_LIO_LISARS-CoV-2 VLP utilizes filopodia to enter target cell via two modes, surfing and grabbing C_LIO_LIFilopodia disruption compromises the invasion of both VLP and authentic SARS-CoV-2 C_LI
ABSTRACT
Effects of "Xuetangping", a herbal prescription composed of Radix Astragali, Radix Trichosanthis, Rhizoma Dioscoreae, Fructus Corni, and Radix Salviae Miltiorrizae, on serum sugar of mice or rats with diabetes mellitus induced by alloxan were studied. The result showed that "Xuetangping" (2.5g/kg, ig qd 7d or 14d ) lowered serum sugar in diabetic mice but not in normal mice.Xuetangpinec 1.5g/kg,ig qd 7d or 14d in diabetic in a dose and time dependent manner. While 14d, "Xuetangping" also decreased the value of serum lipid and the content of serum lipid peroxide. This result suggest that antiperoxide activity of this Chinese herbal formulation may be related to its reduction in serum sugar
ABSTRACT
The infection rate of Oncomelania snails, emergence rate of Schistosoma japa-nicum cercariae, number of emerged cercariae and survival time of infected snails were observed experimentally by exposing single snails to different number of miracidia (i.e. 1, 5, 10, 20 and 40 respectively). The infection rate of snails was shown to be increased with the increasing number of miracidia. The frequency of cercaria emergence of infected snails varied significantly in different seasons and the highest was in spring and summer. No cercaria emergence was observed in winter. The average number of cercariae emerged from a single infected snail in each observation was 70.67, and through the whole lifetime in this experiment, 1,148.85?96.29. There was no significant difference in average number of emerged cercariae among the 5 groups of infected snails. The maximum number of cercariae emerged from one infected snail was 8,079. Calculated from the begining of cercaria emergence, the survival time of infected snails was in average 118.28?9.94 days, and the longest being 839 days. There was no significant difference in survival time among the 5 groups, and 94.8% infected snails died within one year.
