In situ architecture and membrane fusion of SARS-CoV-2 Delta variant.

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.

Firms' exposures on COVID-19 and stock price crash risk: Evidence from China.

This study examines the impact of firms' exposures on COVID-19 sentiment on the stock price crash risk. We show the exposure on COVID-19 sentiment related to the medical, travelling and uncertain aspects significantly increases the stock price crash risk, while the exposure on COVID-19 sentiment related to vaccines significantly decreases the risk of stock price crash. Furthermore, our findings are stronger for non-state-owned firms and firms with low information transparency. Overall, we provide timely policy implication for economic impacts of the COVID-19 on the stock market.

Molecular Architecture of the SARS-CoV-2 Virus.

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.

Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-Derived Extracellular Vesicles.

Pneumonia can cause high morbidity and mortality because of uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to saving the life of patients with severe pneumonia. Here, inspired by the intrinsic affinity of platelets to the site of inflammation, we have engineered platelet-derived extracellular vesicles (PEVs) for pneumonia-targeted drug delivery. It is demonstrated that PEVs that are easily generated from the activated platelets can selectively target pneumonia in the mouse model with acute lung injury (ALI). By loading with [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1), which can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the infiltration of pulmonary inflammatory cells and calming local cytokine storm compared with the free drug-treated group. Furthermore, we find that PEVs could serve as a broad platform that can selectively target various inflammatory sites, including chronic atherosclerotic plaque, rheumatoid arthritis, and wounds associated with skin.