The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral ...RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
We still know very little about how the human immune system responds to SARS-CoV-2. Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to ...the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We find that all these patients had IgG and IgM antibodies that specifically bind SARS-CoV-2 proteins, particularly the N protein and S1 protein. Besides these proteins, significant antibody responses to ORF9b and NSP5 are also identified. We show that the S1 specific IgG signal positively correlates with age and the level of lactate dehydrogenase (LDH) and negatively correlates with lymphocyte percentage. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies.
Background
The missing asymptomatic COVID‐19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in ...asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.
Measure
Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty‐three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS‐CoV‐2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.
Results
A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS‐CoV‐2. Different from strong and persistent N‐specific antibodies, S1‐specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.
Conclusion
Our findings might have important implications for the definition of asymptomatic COVID‐19 infections, diagnosis, serological survey, public health, and immunization strategies.
The combination of NAT and serological testing for IgM antibody significantly improves the detection sensitivity of asymptomatic COVID‐19 infections, compared with NAT alone. S1‐specific IgM antibody response with rapid emergence and disappearance might be helpful to assist NAT for early identification of infectious individuals. A majority of asymptomatics induce very low levels of neutralizing antibody that disappear in two months. Abbreviations: NAT, nucleic acid testing; FI, fluorescence intensity; NT50, half‐maximal neutralizing titer.
To fully decipher the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein, it is essential to assess which part is highly immunogenic in a systematic way. ...We generate a linear epitope landscape of the Spike protein by analyzing the serum immunoglobulin G (IgG) response of 1,051 coronavirus disease 2019 (COVID-19) patients with a peptide microarray. We reveal two regions rich in linear epitopes, i.e., C-terminal domain (CTD) and a region close to the S2′ cleavage site and fusion peptide. Unexpectedly, we find that the receptor binding domain (RBD) lacks linear epitope. We reveal that the number of responsive peptides is highly variable among patients and correlates with disease severity. Some peptides are moderately associated with severity and clinical outcome. By immunizing mice, we obtain linear-epitope-specific antibodies; however, no significant neutralizing activity against the authentic virus is observed for these antibodies. This landscape will facilitate our understanding of SARS-CoV-2-specific humoral responses and might be useful for vaccine refinement.
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•A linear epitope landscape of the SARS-CoV-2 Spike from 1,051 COVID-19 patients•Responsive epitopes are highly variable among patients and correlate with severity•The RBD lacks linear epitopes, but two other regions are rich in linear epitopes•Little neutralization activity is observed for the linear-epitope-elicited antibodies
Li et al. construct a B cell linear epitope landscape of SARS-CoV-2 Spike protein, based on a large cohort of COVID-19 patients. The epitope responses were related to disease severity and outcome but mainly elicit non-neutralizing antibodies.
The first example of paired electrolysis-enabled cyanation of diaryl diselenides, with KSCN as the green cyanating agent, has been developed. A broad range of aryl selenocyanates can be efficiently ...synthesized under chemical-oxidant- and additive-free, energy-saving and mild conditions.
The development of an efficient catalyst for formic acid electrocatalytic oxidation reaction (FAEOR) is of great significance to accelerate the commercial application of direct formic acid fuel cells ...(DFAFC). Herein, palladium phosphide (PdxPy) porous nanotubes (PNTs) with different phosphide content (i.e., Pd3P and Pd5P2) are prepared by combining the self‐template reduction method of dimethylglyoxime‐Pd(II) complex nanorods and succedent phosphating treatment. During the reduction process, the self‐removal of the template and the continual inside–outside Ostwald ripening phenomenon are responsible for the generation of the one‐dimensional hollow and porous architecture. On the basis of the unique synthetic procedure and structural advantages, Pd3P PNTs with optimized phosphide content show outstanding electroactivity and stability for FAEOR. Importantly, the strong electronic effect between Pd and P promotes the direct pathway of FAEOR and inhibits the occurrence of the formic acid decomposition reaction, which effectively enhances the FAEOR electroactivity of Pd3P PNTs. In view of the facial synthesis, excellent electroactivity, high stability, and unordinary selectivity, Pd3P PNTs have the potential to be an efficient anode electrocatalyst for DFAFC.
Efficient formic acid oxidation reaction (FAEOR) electrocatalyst Pd3P porous nanotubes (PNTs) are synthesized by simple self‐template pyrolysis and phosphating treatment. Benefiting from the abundant defect atoms and excellent self‐stability, Pd3P PNTs reveal outstanding electroactivity and durability for FAEOR. The introduction of phosphorus could effectively improve the FAEOR electroactivity of Pd nanomaterials and simultaneously inhibit FADR, highlighting an efficient strategy for designing a DFAFC anode electrocatalyst.
The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid‐electrolyte interphase(SEI) growth would deteriorate its ...stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.
We have given insights into the electron leakage behavior that underlies the distinct SEI growth, by investigating the specific SEI component type/distribution in detail. The uniform SEI layer with favorable component and distribution is found to have both low electron driving force and high electron insulation. Therefore, the electron leakage causing SEI growth is largely restrained.
The majority of people in China have been immunized with the inactivated viral vaccine BBIBP‐CorV. The emergence of the Omicron variant raised the concerns about protection efficacy of the ...inactivated viral vaccine in China. However, longitudinal neutralization data describing protection efficacy against Omicron variant is still lacking. Here we present one‐year longitudinal neutralization data of BBIBP‐CorV on authentic Omicron, Delta, and wild‐type strains using 224 sera collected from 14 volunteers who have finished three doses BBIBP‐CorV. The sera were also subjected for monitoring the SARS‐CoV‐2 specific IgG, IgA, and IgM responses on protein and peptide microarrays. The neutralization titers showed different protection efficacies against the three strains. By incorporating IgG and IgA signals of proteins and Spike protein derived peptide on microarray, panels as potential surrogate biomarkers for rapid estimation of neutralization titers were established. These data support the necessity of the 3rd dose of BBIBP‐CorV vaccination. After further validation and assay development, the panels could be used for reliable, convenient and fast evaluation of the efficacy of vaccination.
An electrochemical multicomponent reaction was established under catalyst-, chemical-oxidant-free and mild conditions, which provides an eco-friendly and simple protocol for constructing ...4-selanylpyrazoles. A broad range of 4-selanylpyrazole derivatives could be obtained from easily available raw materials in good to excellent yields.
An electrochemical multicomponent reaction was established under catalyst-, chemical-oxidant-free and mild conditions, which provides an eco-friendly and simple protocol for constructing 4-selanylpyrazoles from easily available raw materials with high yields.
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