I.A.W.)The outbreak of COVID-19 caused by SARS-CoV-2 virus has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein to 3.1 Å. CR3022 targets a highly conserved epitope, distal from the receptor-binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBD on the trimeric S protein are in the "up" conformation and slightly rotated. Overall, this study provides molecular insights into antibody recognition of SARS-CoV-2.
Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators—including EN-RAGE, TNFSF14, and oncostatin M—which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
Highlights d Cross-reactive antigen binding is common between SARS-CoV and SARS-CoV-2 d Cross-reactive antibody responses target both RBD and non-RBD regions d Cross-neutralization of live viruses may be rare between SARS-CoV and SARS-CoV-2
Background The ongoing coronavirus disease (COVID-19) pandemic has major impacts on health systems, the economy and society. Assessing infection attack rates in the population is critical for estimating disease severity and herd immunity which is needed to calibrate public health interventions. We have previously shown that it is possible to achieve this in real time to impact public health decision making. Aim Our objective was to develop and evaluate serological assays applicable in large-scale sero-epidemiological studies. Methods We developed an ELISA to detect IgG and IgM antibodies to the receptor-binding domain (RBD) of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated its sensitivity and specificity in combination with confirmatory microneutralisation (MN) and 90% plaque reduction neutralisation tests (PRNT90) in 51 sera from 24 patients with virologically confirmed COVID-19 and in age-stratified sera from 200 healthy controls. Results IgG and IgM RBD ELISA, MN and PRNT90 were reliably positive after 29 days from illness onset with no detectable cross-reactivity in age-stratified controls. We found that PRNT90 tests were more sensitive in detecting antibody than MN tests carried out with the conventional 100 tissue culture infectious dose challenge. Heparinised plasma appeared to reduce the infectivity of the virus challenge dose and may confound interpretation of neutralisation test. Conclusion Using IgG ELISA based on the RBD of the spike protein to screen sera for SARS-CoV-2 antibody, followed by confirmation using PRNT90, is a valid approach for large-scale sero-epidemiology studies.
Purpose. This study aims to explore the safety and efficacy of a novel treatment-intense pulsed light (IPL) in MGD eyes. Methods. This study is a prospective and open label study. Forty eyes of 40 MGD patients were recruited in the study and received 4 consecutive IPL treatments on day 1, day 15, day 45, and day 75. Ten ocular surface symptoms were evaluated with a subjective face score at every visit. Best spectacle corrected visual acuity, intraocular pressure (IOP), conjunctival injection, upper and lower tear meniscus height (TMH), tear break-up time (TBUT), corneal staining, lid margin and meibomian gland assessments, and meibography were also recorded at every visit, as well as the adverse effects on the eye and ocular surface. Results. Significant improvements were observed in single and total ocular surface symptom scores, TBUT, and conjunctival injection at all the visits after the initial IPL treatment (P < 0.05). Compared to baseline, the signs of eyelid margin, meibomian gland secretion quality, and expressibility were significantly improved at every visit after treatments. There was no regional and systemic threat observed in any patient. Conclusion. Intense pulsed light (IPL) therapy is a safe and efficient treatment in relieving symptoms and signs of MGD eyes.
Eco-friendly green synthesis with plant extracts plays a very important role in nanotechnology, without any harmful chemicals. In this report, the synthesis of water-soluble silver nanoparticles was developed by treating silver ions with Chrysanthemum morifolium Ramat. extract at room temperature. The effect of the extract on the formation of silver nanoparticles was characterized by ultraviolet and visible absorption spectroscopy, X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. The ultraviolet and visible absorption spectroscopy results show a strong resonance centered on the surface of silver nanoparticles (AgNP) at 430 nm. The Fourier transform infrared spectroscopy spectral study demonstrates Chrysanthemum morifolium Ramat. extract acted as the reducing and stabilizing agent during the synthesis. The X-ray diffraction analysis confirmed that the synthesized AgNP are single crystallines, corresponding with the result of transmission electron microscopy. Water-soluble AgNP, with an approximate size of 20 nm-50 nm were also observed in the transmission electron microscopy image. The bactericidal properties of the synthesized AgNP were investigated using the agar-dilution method and the growth-inhibition test. The results show the AgNP had potent bactericidal activity on Staphylococcus aureus and Escherichia coli, as well as a strong antibacterial activity against gram-negative bacteria, as compared to gram-positive bacteria with a dose-dependent effect, thus providing a clinical ultrasound gel with bactericidal property for prevention of cross infections.
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