Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Coronaviruses”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Benchmark datasets for SARS-CoV-2 surveillance bioinformatics

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spread globally and is being surveilled with an international genome sequencing effort. Surveillance consists of sample acquisition, library preparation, and whole genome sequencing. This has necessitated a classification scheme detailing Variants of Concern (VOC) and Variants of Interest (VOI), and the rapid expansion of bioinformatics tools for sequence analysis. These bioinformatic tools are means for major actionable results: maintaining quality assurance and checks, defining population structure, performing genomic epidemiology, and inferring lineage to allow reliable and actionable identification and classification. Additionally, the pandemic has required public health laboratories to reach high throughput proficiency in sequencing library preparation and downstream data analysis rapidly. However, both processes can be limited by a lack of a standardized sequence dataset. We identified six SARS-CoV-2 sequence datasets from recent publications, public databases and internal resources. In addition, we created a method to mine public databases to identify representative genomes for these datasets. Using this novel method, we identified several genomes as either VOI/VOC representatives or non-VOI/VOC representatives. To describe each dataset, we utilized a previously published datasets format, which describes accession information and whole dataset information. Additionally, a script from the same publication has been enhanced to download and verify all data from this study.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2021

Towards Disentangling Lockdown-Driven Air Quality Changes in the Northeastern U.S.

In the absence of preventive therapies or effective treatment for most cases of coronavirus disease 2019 (COVID-19), governments worldwide have sought to minimize person-to-person severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission through a variety of lock-down measures and social distancing policies. Extreme events like the COVID-19 pandemic present a tremendous opportunity to make quantitative connections between changes in anthropogenic forcing, social and economic activity, and the related Earth system response. In this comment, we examine air quality impacts associated with pandemic response measures in the Northeastern United States.

Air Quality↗
DOE OSTI2020

SLAC joins the global fight against COVID-19

The lab is responding to the coronavirus crisis by imaging disease-related biomolecules, developing standards for reliable coronavirus testing and enabling other essential research.

Gnida, Manuel↗
DOE OSTI2023

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2–3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Models and Processes to Extract Drug-like Molecules From Natural Language Text

Researchers worldwide are seeking to repurpose existing drugs or discover new drugs to counter the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A promising source of candidates for such studies is molecules that have been reported in the scientific literature to be drug-like in the context of viral research. However, this literature is too large for human review and features unusual vocabularies for which existing named entity recognition (NER) models are ineffective. We report here on a project that leverages both human and artificial intelligence to detect references to such molecules in free text. We present 1) a iterative model-in-the-loop method that makes judicious use of scarce human expertise in generating training data for a NER model, and 2) the application and evaluation of this method to the problem of identifying drug-like molecules in the COVID-19 Open Research Dataset Challenge (CORD-19) corpus of 198,875 papers. We show that by repeatedly presenting human labelers only with samples for which an evolving NER model is uncertain, our human-machine hybrid pipeline requires only modest amounts of non-expert human labeling time (tens of hours to label 1778 samples) to generate an NER model with an F-1 score of 80.5%—on par with that of non-expert humans—and when applied to CORD’19, identifies 10,912 putative drug-like molecules. This enriched the computational screening team’s targets by 3,591 molecules, of which 18 ranked in the top 0.1% of all 6.6 million molecules screened for docking against the 3CLPro protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Differential contagiousness of respiratory disease across the United States

The initial contagiousness of a communicable disease within a given population is quantified by the basic reproduction number, $R_0$. This number depends on both pathogen and population properties. On the basis of compartmental models that reproduce Coronavirus Disease 2019 (COVID-19) surveillance data, we used Bayesian inference and the next-generation matrix approach to estimate region-specific $R_0$ values for 280 of 384 metropolitan statistical areas (MSAs) in the United States (US), which account for 95% of the US population living in urban areas and 82% of the total population. We focused on MSA populations after finding that these populations were more uniformly impacted by COVID-19 than state populations. Our maximum a posteriori (MAP) estimates for $R_0$ range from 1.9 to 7.7 and quantify the relative susceptibilities of regional populations to spread of respiratory diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A time-varying vulnerability index for COVID-19 in New Mexico, USA using generalized propensity scores

The coronavirus disease (COVID-19) pandemic has highlighted systemic inequities in the United States and resulted in a larger burden of negative social outcomes for marginalized communities. New Mexico, a state in the southwestern US, has a unique population with a large racial minority population and a high rate of poverty that may make communities more vulnerable to negative social outcomes from COVID-19. To identify which communities may be at the highest relative risk, we created a county-level vulnerability index. After the first COVID-19 case was reported in New Mexico on March 11, 2020, we fit a generalized propensity score model that incorporates sociodemographic factors to predict county-level viral exposure and thus, the generic risk to negative social outcomes such as unemployment or mental health impacts. We used four static sociodemographic covariates important for the state of New Mexico—population, poverty, household size, and minority population—and weekly cumulative case counts to iteratively run our model each week and normalize the exposure score to create a time-varying vulnerability index. We found the relative vulnerability between counties varied in the first eight weeks from the initial COVID-19 case before stabilizing. This framework for creating a location-specific vulnerability index in response to an ongoing disaster may be used as a quick, deployable metric to inform health policy decisions such as allocating state resources to the county level.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Clinician Attitudes to Using Low-Dose Radiation Therapy to Treat COVID-19 Lung Disease

Current treatments for coronavirus disease 2019 (COVID-19) lung disease have limited efficacy. Low-dose radiation therapy (LDRT) has received both interest and criticism as a potential treatment for this condition. In this qualitative study we explored clinicians’ perspectives to identify barriers to testing LDRT in clinical trials and implementing it in clinical practice.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Low Doses of Radiation Increase the Immunosuppressive Profile of Lung Macrophages During Viral Infection and Pneumonia

Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Differential Impact of COVID-19 on Cancer Diagnostic Services Based on Body Regions: A Public Facility-Based Study in Hong Kong

A reduction in cancer services during the coronavirus disease of 2019 pandemic has affected cancer diagnoses. The purpose of this study is to quantitatively determine the impact on cancer diagnostic service in public facilities across Hong Kong. Quantifying the temporal changes in the number of cancer diagnoses before, during, and after the outbreak is useful to establish the scale of the problem and assess if there has been an adequate level of response.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Benchmarking Concentration and Extraction Methods for Wastewater-Based Surveillance of Eight Human Respiratory Viruses: Implications for Rapid Application to Novel Pathogens

To provide early warning and support a rapid response to a novel virus through wastewater surveillance, it would be ideal to understand in advance which concentration and extraction methods are likely to be effective for dPCR-based methods, depending on virus characteristics. In this study, we spiked raw wastewater samples with eight human respiratory viruses and processed them with four methods that concentrate and/or extract nucleic acids from both liquid and solid fractions (Promega, Nanotrap, and InnovaPrep) or only the solid fraction of wastewater (Solids). Our findings provide encouraging evidence that all four methods combined with dPCR could detect an emerging virus in wastewater, although they differed in sensitivity. The pattern of recovery efficiency for adenoviruses, coronaviruses, and influenza A viruses was consistent across methods, with Promega producing higher median recovery efficiencies, while distinct patterns were observed for coxsackieviruses. We also normalized the concentration data with two endogenous fecal indicators, PMMoV and Carjivirus (formerly crAssphage). We found that normalization could reduce method-associated differences if the indicator exhibited a recovery pattern similar to that of the target virus. These findings can guide the selection of concentration and extraction methods for wastewater monitoring based on the properties of target viruses, thus enhancing pandemic preparedness.

Biological and medical sciences↗
DOE OSTI2021

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2

The coronavirus disease 2019 (COVID-19) outbreak has devastated the healthcare systems and economies of over 200 countries in just a few months. The etiological agent of COVID-19, SARS-CoV-2, is a highly contagious virus that can be transmitted by asymptomatic and symptomatic carriers alike. While in vitro testing techniques have allowed for population-wide screening, prognostic tools are required to assess the disease severity and therapeutic response, contributing to improve the patient clinical outcomes. Moreover, no specific antiviral against COVID-19 exists at the time of publication, severely limiting treatment against the infection. Hence, there is an urgent clinical need for innovative therapeutic strategies that may contribute to manage the COVID-19 outbreak and prevent future pandemics. In this work, we critically examine recent diagnostic, prognostic, and therapeutic advancements for COVID-19 in the field of radiopharmaceuticals. First, we summarize the gold standard techniques used to diagnose COVID-19, including in vitro assays and imaging techniques, and then discuss how radionuclide-based nuclear imaging provides complementary information for prognosis and treatment management of infected patients. Second, we introduce new emerging types of radiotherapies that employ radioimmunoconjugates, which have shown selective cytotoxic response in oncological studies, and critically analyze how these compounds could be used as therapeutic agents against SARS-CoV-2. Finally, this Perspective further discusses the emerging applications of radionuclides to study the behavior of pulmonary SARS-CoV-2 aerosol particles.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2023

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2

The nonstructural protein 3 (NSP3) of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) contains a conserved macrodomain enzyme (Mac1) that is critical for pathogenesis and lethality. While small-molecule inhibitors of Mac1 have great therapeutic potential, at the outset of the COVID-19 pandemic, there were no well-validated inhibitors for this protein nor, indeed, the macrodomain enzyme family, making this target a pharmacological orphan. Here, we report the structure-based discovery and development of several different chemical scaffolds exhibiting low- to sub-micromolar affinity for Mac1 through iterations of computer-aided design, structural characterization by ultra-high-resolution protein crystallography, and binding evaluation. Potent scaffolds were designed with in silico fragment linkage and by ultra-large library docking of over 450 million molecules. Both techniques leverage the computational exploration of tangible chemical space and are applicable to other pharmacological orphans. Overall, 160 ligands in 119 different scaffolds were discovered, and 153 Mac1-ligand complex crystal structures were determined, typically to 1 Å resolution or better. Our analyses discovered selective and cell-permeable molecules, unexpected ligand-mediated conformational changes within the active site, and key inhibitor motifs that will template future drug development against Mac1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Multi-species outbreak of SARS-CoV-2 Delta variant in a zoological institution, with the detection in two new families of carnivores

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a worldwide distribution in humans and many other mammalian species. In late September 2021, 12 animals maintained by the Chicago Zoological Society's Brookfield Zoo were observed with variable clinical signs. The Delta variant of SARS-CoV-2 was detected in faeces and nasal swabs by qRT-PCR, including the first detection in animals from the families Procyonidae and Viverridae. Test positivity rate was 12.5% for 35 animals tested. All animals had been vaccinated with at least one dose of a recombinant vaccine designed for animals and all recovered with variable supportive treatment. Sequence analysis showed that six zoo animal strains were closely correlated with 18 human SARS-CoV-2 strains, suggestive of potential human-to-animal transmission events. This report documents the expanding host range of COVID-19 during the ongoing pandemic.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy complementarity-determining region 3 (HCDR3) loop into a hydrophobic NTD cavity previously shown to bind a heme metabolite, biliverdin. We demonstrate direct competition with biliverdin and that, because of the conserved nature of the epitope, the mAb maintains binding to viral variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Our study describes a novel conserved epitope on the NTD that is readily targeted by vaccine-induced antibody responses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody

Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses.

59 BASIC BIOLOGICAL SCIENCES↗