The COVID-19 dashboard includes data on city/town COVID-19 activity, confirmed and probable cases of COVID-19, confirmed and probable deaths related to COVID-19, and the demographic characteristics of cases and deaths.
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COVID-19 pandemics has led to genetic diversification of SARS-CoV-2 and the appearance of variants with potential impact in transmissibility and viral escape from acquired immunity. We report a new and highly divergent lineage containing 21 distinctive mutations (10 non-synonymous, eight synonymous, and three substitutions in non-coding regions). The amino acid changes L249S and E484K located at the CTD and RBD of the Spike protein could be of special interest due to their potential biological role in the virus-host relationship. Further studies are required for monitoring the epidemiologic impact of this new lineage.
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Coronaviruses (CoVs) [E1] are a diverse group of enveloped, plus-stranded RNAviruses that infect humans and many animal species, in which they can causerespiratory, enteric, hepatic, central nervous system and neurologicaldiseases of varying severity. A CoV contains four structural proteins,including spike (S), envelope (E), membrane (M), and nucleocapsid (N)proteins. Among them, the S protein, which is located on the envelope surfaceof the virion, functions to mediate receptor recognition and membrane fusionand is therefore a key factor determining the virus tropism for a specificspecies. This protein is composed of an N-terminal receptor-binding domain(S1) and a C-terminal trans-membrane fusion domain (S2) .The S2 subunit contains two 4-3 heptad repeats (HRs) of hydrophobic residues,HR1 and HR2, typical of coiled coils, separated by an ~170-aa-long interveningdomain. The S2 subunit is expected to present rearrangement of its HRs to forma stable 6-helix bundle fusion core .HR1 forms a 24-turn alpha-helix, while HR2 adopts a mixed conformation: thecentral part fold into a nine-turn alpha-helix, while the residues on eitherside of the helix adopt an extended conformation. The HR1 region forms a longtrimeric helical coiled-coil structure with peptides from the HR2 regionpacking in an oblique antiparallel manner on the grooves of the HR1 trimer ina mixed extended and helical conformation. Packing of thehelical parts of HR2 on the HR1 trimer grooves and formation of a six-helicalbundle plays an important role in the formation of a stable post-fusionstructure. In contrast to their extended helical conformations in the post-fusion state, the HR1 motifs within S2 form several shorter helices in theirpre-fusion state .The profiles we developed cover the entire CoV S2-HR1 -HR2 regions.
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To assess spike mutation impact on ACE2 binding, fusogenicity, and neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus.
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PDBs were generated using molecular dynamics. See DESRES_README.txt for more details on molecular dynamics simulation. PDBs were converted to volumetric data using EMAN2. The image stack contains 100 000 projection images each of the 10 states (see PDBs), at an SNR of 1/10 in the following order:
state00 (closed) state01 (closed) state02 (closed) state10 (intermediate) state11 (intermediate) state12 (intermediate) state13 (intermediate) state20 (open) state21 (open) state22 (open)
Projections were made using relion_project. White gaussian noise with standard deviation 1.0 CTF multiplied signal High signal-to-noise ratio Image size 96x96x96
MRC-files used for the projections not included, but can be generated using the PDB files. Final RELION reconstruction resolution is 5.33334 Angstrom (Nyqvist is at 5.33334).
Command line for RELION reconstruction: relion_refine_mpi --o refine3d/run --auto_refine --split_random_halves --i rot_trans_ctf_noise/stack.star --ref pdb2mrc/state21.mrc --ini_high 20 --dont_combine_weights_via_disc --preread_images --pool 30 --pad 2 --ctf --particle_diameter 130 --flatten_solvent --zero_mask --oversampling 1 --healpix_order 2 --auto_local_healpix_order 4 --offset_range 5 --offset_step 2 --low_resol_join_halves 40 --norm --scale --j 2 --gpu --fristiter_cc --grad
This dataset is generated as a testbed for cryo-EM heterogeneity analysis.
The New York Times is releasing a series of data files with cumulative counts of coronavirus cases in the United States, at the state and county level, over time. We are compiling this time series data from state and local governments and health departments in an attempt to provide a complete record of the ongoing outbreak.
Since late January, The Times has tracked cases of coronavirus in real time as they were identified after testing. Because of the widespread shortage of testing, however, the data is necessarily limited in the picture it presents of the outbreak.
We have used this data to power our maps and reporting tracking the outbreak, and it is now being made available to the public in response to requests from researchers, scientists and government officials who would like access to the data to better understand the outbreak.
The data begins with the first reported coronavirus case in Washington State on Jan. 21, 2020. We will publish regular updates to the data in this repository.
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The map shows the 7-day incidence of confirmed cases of COVID-19 in the Austrian districts on a daily basis since the data were available (26 February 2020) and puts them in relation to the political targets.
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The coronavirus spike is an envelope glycoprotein which aids viral entry into the host cell. The precursor spike protein can be cleaved into three chains: spike protein S1, S2 and S2'. Spike protein S1 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Spike protein S2 mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Spike protein S2' acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis .S1 contains two major domains: an N-terminal domain (NTD) and a receptor-binding domain (S1 RBD) also referred to as the S1 CTD or domain B. Either the S1 NTD or S1 RBD, or occasionally both, are involved in binding the host receptors .
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To evaluate the neutralization and binding activities of sera collected from COVID-19 mRNA vaccine recipients against current SARS-CoV-2 Variants of Concern/Interest.
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The type I glycoprotein S of Coronavirus, trimers of which constitute the typical viral spikes, is assembled into virions through noncovalent interactions with the M protein. The spike glycoprotein is translated as a large polypeptide that is subsequently cleaved to S1 ([interpro:IPR002551]) and S2 . The cleavage of S can occur at two distinct sites: S2 or S2' . The spike is present in two very different forms: pre-fusion (the form on mature virions) and post-fusion (the form after membrane fusion has been completed). The spike is cleaved sequentially by host proteases at two sites: first at the S1/S2 boundary (i.e. S1/S2 site) and second within S2 (i.e. S2' site). After the cleavages, S1 dissociates from S2, allowing S2 to transition to the post-fusion structure . Both chimeric S proteins appeared to cause cell fusion when expressed individually, suggesting that they were biologically fully active . The spike is a type I membrane glycoprotein that possesses a conserved transmembrane anchor and an unusual cysteine-rich (cys) domain that bridges the putative junction of the anchor and the cytoplasmic tail .SARS-CoV S is largely uncleaved after biosynthesis. It can be later processed by endosomal cathepsin L, trypsin, thermolysin, and elastase, which are shown to induce syncytia formation and virus entry. Other proteases that are of potential biological relevance in potentiating SARS-CoV S include TMPRSS2, TMPRSS11a, and HAT which are localized on the cell surface and are highly expressed in the human airway . The furin-like S2' cleavage site at KR/SF with P1 and P2 basic residues and a P2' hydrophobic Phe downstream of the IFP is identical between the SARS-CoV-2 and SARS-CoV. One or more furin-like enzymes would cleave the S2' site at KR/SF . Deletion of SARS-CoV-2 furin cleavage site suggests that it may not be required for viral entry but may affect replication kinetics and altered sites have been still seen proteolytically cleaved. Several substitutions within the S2' cleavage domain of SARS-COV-2 have been reported, including P812L/S/T, S813I/G, F817L, I818S/V, but further experimental study of their consequences and the replication properties of the altered viruses are required to understand the role of furin cleavage in SARS-CoV-2 infection and virulence .
The dataset of spike Covid proteins was obtained from GISAID. Each protein in the dataset is represented as a sequence of amino acids (AAs).
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Background: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. Methods: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children's Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2-specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2-specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. Results: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P<0.0001). Conclusions: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine-induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.
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The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus since its emergence in 2019 has yielded several new viral variants with varied infectivity, disease severity, and antigenicity. Although most mutations are expected to be relatively neutral, mutations at the Spike region of the genome have shown to have a major impact on the viral transmission and infection in humans. Therefore, it is crucial to survey the structures of spike protein across the global virus population to contextualize the rate of therapeutic success against these variants. In this study, high-frequency mutational variants from different geographic regions were pooled in order to study the structural evolution of the spike protein through drug docking and MD simulations. We investigated the mutational burden in the spike subregions and have observed that the different variants harbour unique signature patterns in the spike subregions, with certain domains being highly prone to mutations. Further, the MD simulations and docking study revealed that different variants show differential stability when docked for the same set of drug targets. This work sheds light on the mutational burden and the stability landscape of the spike protein across the variants from different geographical regions. Communicated by Ramaswamy H. Sarma
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As of November 11, 2022, almost 96.8 million confirmed cases of COVID-19 had been reported by the World Health Organization (WHO) for the United States. The pandemic has impacted all 50 states, with vast numbers of cases recorded in California, Texas, and Florida.
The coronavirus in the U.S. The coronavirus hit the United States in mid-March 2020, and cases started to soar at an alarming rate. The country has performed a high number of COVID-19 tests, which is a necessary step to manage the outbreak, but new coronavirus cases in the U.S. have spiked several times since the pandemic began, most notably at the end of 2022. However, restrictions in many states have been eased as new cases have declined.
The origin of the coronavirus In December 2019, officials in Wuhan, China, were the first to report cases of pneumonia with an unknown cause. A new human coronavirus – SARS-CoV-2 – has since been discovered, and COVID-19 is the infectious disease it causes. All available evidence to date suggests that COVID-19 is a zoonotic disease, which means it can spread from animals to humans. The WHO says transmission is likely to have happened through an animal that is handled by humans. Researchers do not support the theory that the virus was developed in a laboratory.
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To describe a sensitive and reliable SARS-CoV-2 S�bearing lentivirus inGluc neutralization assay that is validated by the authentic SARS-CoV-2 plaque-reduction assay
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To examine the ability of vaccine-induced antibodies to drive Fc effector activity against Omicron variant using samples from individuals receiving BNT162b2, mRNA-1273 or CoronaVac vaccination
Research on COVID-19 vaccination in immune-deficient/disordered people (IDP) has primarily focused on cancer and organ transplantation populations. In a prospective cohort of 195 IDP and 35 healthy volunteers, anti-spike IgG was detected in 88% of IDP post-dose 2, increasing to 93% by six months post-dose 3. Despite high seroconversion, median IgG levels for IDP never surpassed 1/3 that of healthy volunteers. IgG binding to Omicron BA.1 was lower than all other variants. Angiotensin-converting enzyme 2 pseudo-neutralization (% inhibition) was only modestly correlated with anti-spike IgG concentration. IgG levels were not significantly altered by participants’ use of different mRNA-based vaccines, immunomodulating treatments, and prior SARS-CoV-2 infections. While our data show that three doses of COVID-19 vaccinations induce anti-spike IgG in most IDP, additional doses are needed to achieve the levels of protection in healthy volunteers. Due to the strikingly reduced IgG response to Omi..., All methods for the collection and processing of these data are published in the associated manuscript. Code and survey instruments are available at https://doi.org/10.5281/zenodo.8428160., , # Characterization of the anti-spike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies
https://doi.org/10.5061/dryad.6hdr7sr68
This data was collected as part of the PERSIST cohort study (NCT04852276), which aimed to assess the immune response to COVID-19 vaccines in people with immune disorders and healthy volunteers. We collected and analyzed data from April 2021 through April 2022 for this study. Laboratory methods that describe the assay specifics can be found in the associated publication, “Characterization of the anti-spike IgG immune response to COVID-19 vaccines in people with a wide variety of immunodeficiencies†in Science Advances.  Five unique datasets were used in our study. Four datasets were derived from participant data:
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This repository contains the molecular dynamics trajectories of the SARS-CoV-2 Spike RBD bound to BD23 and B38 monoclonal antibodies. The simulations for the RBD only systems are also provided. The trajectories are available for the WT spike protein as well as for four different variants (alpha, beta, kappa and delta). The simulations of the RBD only system are propagated for 300 ns and for the RBD-Antibody complex for 500 ns. The trajectories are saved at 100 ps interval. The Steered MD simulation trajectories (WT_RBD_B38_SMD_1.dcd etc.) and collective variables files are also included (WT_RBD_B38_SMD_1.colvars.traj etc.). There are 5 SMD trajectories for each RBD antibody pair. The details of the simulation can be obtained from the preprint: https://doi.org/10.1101/2021.08.13.456317
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Production and purification of recombinant receptor-binding domain (RBD) of the Spike protein from a transiently transfected EXPI293 mammalian cell .
The COVID-19 dashboard includes data on city/town COVID-19 activity, confirmed and probable cases of COVID-19, confirmed and probable deaths related to COVID-19, and the demographic characteristics of cases and deaths.