a new coronavirus emerged in China and caused an acute respiratory disease now known as coronavirus disease 2019 (COVID-19) (1). The virus was identified to be a betacoronavirus related to severe acute respiratory syndrome coronavirus (SARS-CoV) and thus was named SARS-CoV-2 (2). In <2 decades, this virus is the third known coronavirus to cross the species barrier and cause severe respiratory infections in humans after SARS-CoV in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, yet with unprecedented spread compared with the earlier 2 viruses.Because of the rapid increase in number of cases and uncontrolled and vast spread worldwide, the World Health Organization has declared SARS-CoV-2 a pandemic. As of March 14, 2020, the virus had infected >130,000 persons in 122 countries, 3.7% of whom had died. (3). Rapid identification of the etiology and sharing of the genetic sequence of the virus, followed by international collaborative efforts initiated because of emergence of SARS-CoV-2, has led to rapid availability of real-time PCR diagnostic assays that support case ascertainment and tracking of the outbreak (4). Availability of these assays has helped in patient detection and efforts to contain the virus. However, validated serologic assays are still lacking and are urgently needed.Validated serologic assays are crucial for patient contact tracing, identifying the viral reservoir hosts, and epidemiologic studies. Epidemiologic studies are urgently needed to help uncover the burden of disease, in particular the rate of asymptomatic infections, and to get better estimates on illness and death. In ad-
The thermal decomposition of lithium-ion battery electrolytes 1.0M LiPnormalF6 in one or more carbonate solvents has been investigated. Electrolytes containing diethyl carbonate (DEC), ethylene carbonate (EC), a 1:1 mixture of EC/dimethyl carbonate (DMC), and a 1:1:1 mixture EC/DMC/DEC have been investigated by multinuclear nuclear magnetic spectroscopy, gas chromatography with mass selective detection, and size exclusion chromatography. Thermal decomposition affords products including: carbon dioxide (CnormalO2) , ethylene (CnormalH2CnormalH2) , dialkylethers (normalR2O) , alkyl fluorides (RF), phosphorus oxyfluoride (OPnormalF3) , fluorophosphates [OPnormalF2OR,OPF(OR)2] , fluorophosporic acids [OPnormalF2OH,OPF(OH)2] , and oligoethylene oxides. The mechanism of decomposition is similar in all LiPnormalF6 /carbonate electrolytes. Trace protic impurities lead to generation of OPnormalF2OR , which autocatalytically decomposes LiPnormalF6 and carbonates. The presence of DEC leads to the generation of ethylene, while the presnce of EC leads to the generation of capped oligothylene oxides [OPnormalF2(OCnormalH2CnormalH2)nF] .
Three structurally identical polymers, except for the number of fluorine substitutions (0, 1, or 2) on the repeat unit (BnDT-DTBT), are investigated in detail, to further understand the impact of these fluorine atoms on open circuit voltage (V(oc)), short circuit current (J(sc)), and fill factor (FF) of related solar cells. While the enhanced V(oc) can be ascribed to a lower HOMO level of the polymer by adding more fluorine substituents, the improvement in J(sc) and FF are likely due to suppressed charge recombination. While the reduced bimolecular recombination with raising fluorine concentration is confirmed by variable light intensity studies, a plausibly suppressed geminate recombination is implied by the significantly increased change of dipole moment between the ground and excited states (Δμ(ge)) for these polymers as the number of fluorine substituents increases. Moreover, the 2F polymer (PBnDT-DTffBT) exhibits significantly more scattering in the in-plane lamellar stacking and out-of-plane π-π stacking directions, observed with GIWAXS. This indicates that the addition of fluorine leads to a more face-on polymer crystallite orientation with respect to the substrate, which could contribute to the suppressed charge recombination. R-SoXS also reveals that PBnDT-DTffBT has larger and purer polymer/fullerene domains. The higher domain purity is correlated with an observed decrease in PCBM miscibility in polymer, which drops from 21% (PBnDT-DTBT) to 12% (PBnDT-DTffBT). The disclosed "fluorine" impact not only explains the efficiency increase from 4% of PBnDT-DTBT (0F) to 7% with PBnDT-DTffBT (2F) but also suggests fluorine substitution should be generally considered in the future design of new polymers.
The threat of a major coronavirus pandemic urges the development of suitable strategies to combat these pathogens. HCoV-NL63 is an α-coronavirus that can cause severe lower respiratory tract infections requiring hospitalization. We report here the 3.4 Å resolution cryo-electron microscopy reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which is the conformational machine responsible for entry into host cells and the sole target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass-spectrometry, provides a structural framework to understand accessibility to antibodies. The structure also reveals a remarkable modular architecture of the receptor-binding subunit and the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on masking of epitopes with glycans and activating conformational changes, to evade the immune system of infected hosts.
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1 through S1 Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1 We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia). Initially demonstrated by hemagglutination assay with human erythrocytes and intact virus, MERS-CoV Sia-binding activity was assigned to S subdomain S1 When multivalently displayed on nanoparticles, S1 or S1 bound to human erythrocytes and to human mucin in a strictly Sia-dependent fashion. Glycan array analysis revealed a preference for α2,3-linked Sias over α2,6-linked Sias, which correlates with the differential distribution of α2,3-linked Sias and the predominant sites of MERS-CoV replication in the upper and lower respiratory tracts of camels and humans, respectively. Binding is hampered by Sia modifications such as 5--glycolylation and (7,)9--acetylation. Depletion of cell surface Sia by neuraminidase treatment inhibited MERS-CoV entry of Calu-3 human airway cells, thus providing direct evidence that virus-Sia interactions may aid in virion attachment. The combined observations lead us to propose that high-specificity, low-affinity attachment of MERS-CoV to sialoglycans during the preattachment or early attachment phase may form another determinant governing the host range and tissue tropism of this zoonotic pathogen.
Human betacoronaviruses OC43 and HKU1 are endemic respiratory pathogens and, while related, originated from independent zoonotic introductions. OC43 is in fact a host-range variant of the species Betacoronavirus-1, and more closely related to bovine coronavirus (BCoV)-its presumptive ancestor-and porcine hemagglutinating encephalomyelitis virus (PHEV). The β1-coronaviruses (β1CoVs) and HKU1 employ glycan-based receptors carrying 9-Oacetylated sialic acid (9-O-Ac-Sia). Receptor binding is mediated by spike protein S, the main determinant of coronavirus host specificity. For BCoV, a crystal structure for the receptor-binding domain S1 A is available and for HKU1 a cryoelectron microscopy structure of the complete S ectodomain. However, the location of the receptorbinding site (RBS), arguably the single-most important piece of information, is unknown. Here we solved the 3.0-Å crystal structure of PHEV S1 A . We then took a comparative structural analysis approach to map the β1CoV S RBS, using the general design of 9-O-Ac-Siabinding sites as blueprint, backed-up by automated ligand docking, structure-guided mutagenesis of OC43, BCoV, and PHEV S1 A , and infectivity assays with BCoV-S-pseudotyped vesicular stomatitis viruses. The RBS is not exclusive to OC43 and related animal viruses, but is apparently conserved and functional also in HKU1 S1 A . The binding affinity of the HKU1 S RBS toward short sialoglycans is significantly lower than that of OC43, which we attribute to differences in local architecture and accessibility, and which may be indicative for differences between the two viruses in receptor finespecificity. Our findings challenge reports that would map the OC43 RBS elsewhere in S1 A and that of HKU1 in domain S1 B .coronavirus | spike | 9-O-acetylated sialic acid | OC43 | HKU1 C oronaviruses (CoVs; order Nidovirales, family Coronaviridae) are enveloped positive-strand RNA viruses of mammals and birds. So far, four coronaviruses of zoonotic origin are known to have successfully breached the species barrier to become true human pathogens (1-6). These viruses-NL63, 229E, HKU1, and OC43-are persistently maintained in the human population through continuous circulation. Remarkably, the latter two both belong to a single minor clade, "lineage A," in the genus Betacoronavirus. Although generally associated with common colds, HKU1 and OC43 may cause severe and sometimes fatal pulmonary infections in the frail (7, 8), and in rare instances, OC43 may cause lethal encephalitis (9). OC43 and HKU1 are distinct viruses that entered the human population independently to seemingly follow convergent evolutionary trajectories in their adaptation to the novel host (10). OC43 is in fact more related to coronaviruses of ruminants, horses, dogs, rabbits, and swine, with which it has been united in a single species, Betacoronavirus-1.Lineage A betacoronaviruses like HKU1 and OC43 differ from other CoVs in that their virions possess two types of surface projections, both of which are involved in attachment: large 20-nm peplomer...
A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic.Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike-and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCRconfirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.
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