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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.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Development of a rapid viability RT-PCR (RV-RT-PCR) method to detect infectious SARS-CoV-2 from swabs

Since the rapid onset of the COVID-19 pandemic, its causative virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), continues to spread and increase the number of fatalities. To expedite studies on understanding potential surface transmission of the virus and to aid environmental epidemiological investigations, here we developed a rapid viability reverse transcriptase PCR (RV-RT-PCR) method that detects viable (infectious) SARS-CoV-2 from swab samples in <1 day compared to several days required by current gold-standard cell-culture-based methods. The method integrates cell-culture-based viral enrichment in a 96-well plate format with gene-specific RT-PCR-based analysis before and after sample incubation to determine the cycle threshold (C T ) difference (ΔC T ). An algorithm based on ΔC T ≥ 6 representing ~ 2-log or more increase in SARS-CoV-2 RNA following enrichment determines the presence of infectious virus. The RV-RT-PCR method with 2-hr viral infection and 9-hr post-infection incubation periods includes ultrafiltration to concentrate virions, resulting in detection of <50 SARS-CoV-2 virions in swab samples in 17 h (for a batch of 12 swabs), compared to days typically required by the cell-culture-based method. The SARS-CoV-2 RV-RT-PCR method may also be useful in clinical sample analysis and antiviral drug testing, and could serve as a model for developing rapid methods for other viruses of concern.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Efficacy of antivirals and mRNA vaccination against an XBF clinical isolate

Recombination events occur frequently in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in genetic diversity. Because these events contribute to altered host immune evasion and antiviral susceptibility, it is crucial to evaluate the efficacy of COVID-19 vaccines and antivirals against recombinant variants. As of March 2023, XBB.1.5, a recombinant sublineage of XBB, is currently the dominant form globally (Fig. S1A, Supplementary Appendix). XBB emerged as a result of recombination between two BA.2 descendants, BJ.1 and BM.1.1.1 (a progeny of BA.2.75). We and other groups have shown that XBB.1.5 is resistant to several therapeutic monoclonal antibodies and effectively evades humoral immunity elicited by natural infection or COVID-19 vaccination.1, 2, 3 By March 30, 2023, an additional recombinant variant, XBF, had been sampled 8966 times in 47 countries and territories in GISAID, reaching it highest prevalence in Australia and New Zealand (Fig. S2, Supplementary Appendix). XBF is still increasing in frequency, although the prevalence of XBB.1.5 appears to be increasing at a faster pace in most regions (Fig. S1B, Supplementary Appendix). XBF is a recombinant of BA.5.2.3 (a descendant of BA.5) and CJ.1 (a descendant of BA.2.75) and, like CJ.1, has an additional three substitutions (R346T, F486P, and F490S) in the receptor-binding domain (RBD) of the consensus form of its spike protein compared to baseline BA.2.75 (Fig. S3A, Supplementary Appendix). CJ.1 and its related sublineage CJ.1.1 did not expand as extensively as XBF, being sampled in GISAID only 1589 and 142 times respectively. CJ.1 was found circulating in many countries, but most commonly sampled in South Korea, where it is still increasing and has currently reached about 5% of the sampled population. CJ.1.1 was most frequently sampled in Malaysia and Singapore, but remained rare in both nations, peaking at about 1% of the sample in December of 2022. Despite the importance of these related variants, we have no information about the antiviral efficacy and immunity induced by COVID-19 vaccines against a clinical isolate of XBF.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Effective antiviral coatings for deactivating SARS-CoV-2 virus on N95 respirator masks or filters

The application of antiviral coatings to masks and respirators is a potential mitigating step toward reducing viral transmission during the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic. The use of appropriate masks, social distancing, and vaccines is the immediate solution for limiting the viral spread and protecting people from this virus. N95 respirator masks are effective in filtering the virus particles, but they cannot kill or deactivate the virus. We report a possible approach to deactivating SARS-CoV-2 by applying an antimicrobial coating (Goldshield 75) to masks and respirators, rendering them suitable for repeated use. Masks coated with Goldshield 75 demonstrated continuous inactivation of the Alpha and Beta variants of the SARS-CoV-2 over a 3-day period and no loss of inactivation when stored at temperatures at 50 °C.

36 MATERIALS SCIENCE↗
DOE OSTI2024

Protein data bank: From two epidemics to the global pandemic to mRNA vaccines and Paxlovid

Structural biologists and the open-access Protein Data Bank (PDB) played decisive roles in combating the COVID-19 pandemic. Global biostructure data were turned into global knowledge, allowing scientists and engineers to understand the inner workings of coronaviruses and develop effective countermeasures. Two mRNA vaccines, initially designed with guidance from PDB structures of the SARS-CoV-1 and MERS-CoV spike proteins, prevented infections entirely or reduced the likelihood of morbidity and mortality for more than five billion individual recipients worldwide. Structure-guided drug discovery by Pfizer, Inc (facilitated by PDB structures), initiated in the 2000s in response to SARS-CoV-1 and resumed in 2020, yielded nirmatrelvir (the active ingredient of Paxlovid) -- a potent, orally-bioavailable inhibitor of the SARS-CoV-2 main protease. You've got to love the Protein Data Bank!

Burley, Stephen K.↗
DOE OSTI2021

Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV-2.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Adoption of delivery services in light of the COVID pandemic: Who and how long?

A significant growth in demand for online shopping in light of the Coronavirus Disease (COVID) crisis has received attention from transportation practitioners, policy-makers, and researchers. However, an important question arises in this increase in online shopping and resulting deliveries: How long will this last? Very little is known whether this popularity would last a long time. Here, to address this question, the authors conducted a survey of 915 individuals residing in the U.S. and classified them into the four distinctive consumer types (i.e., the prior adopter, temporary adopter and permanent new adopter, and non-adopter) depending on their usage of delivery services before, during, and after (expected) the COVID crisis. This research aims to gain behavioral insight by exploring the differences between the four consumer types and investigating factors affecting the initial adoption and continuance intention of using delivery services. The descriptive analysis revealed that there are clear differences not only between the four types of consumers but also between the four product types (i.e., grocery, food, home goods, and other packages) considered in the survey. The models found that factors affecting the initial adoption and continuance intention are different from the previous studies conducted before the COVID pandemic. Implications for planning and policymaking are also discussed.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2023

Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that BA.2.86 might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show that NAb titers are substantially lower to BA.2.86 compared with BA.2 but are similar or slightly higher than to other current circulating variants, including XBB.1.5, EG.5.1, and FL.1.5.1. Moreover, NAb titers against all these variants were higher in vaccinated individuals with a history of XBB.1.5 infection compared with vaccinated individuals with no history of XBB.1.5 infection, suggesting the potential utility of the monovalent XBB.1.5 mRNA boosters.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

A modeling pipeline to relate municipal wastewater surveillance and regional public health data

As COVID-19 becomes endemic, public health departments require improved passive indicators, which are independent of voluntary testing data, to estimate the prevalence of COVID-19 in local communities. Quantification of SARS-CoV-2 RNA from wastewater has the potential to be a powerful passive indicator. However, connecting measured SARS-CoV-2 RNA to community prevalence is challenging. We have developed a generalized methodology to improve the predictive power of wastewater measurements and applied it to data collected from treatment plants in the Chicago area. We built and compared a set of multi-linear regression models, which incorporate pepper mild mottle virus (PMMoV) as a population biomarker, Bovine coronavirus (BCoV) as a recovery control, and wastewater system flow rate into a corrected estimate for SARS-CoV-2 RNA concentration. For our data, models with BCoV performed better than those with PMMoV, but all model estimates of prevalence significantly improved correlation compared to doing no correction. We also investigate the utility of RNA measurements in wastewater as a leading indicator of COVID-19 trends. We do this in a rolling manner for corrected wastewater data and for other prevalence indicators, and statistically compare the temporal relationship between new increases in the wastewater data and those in other prevalence indicators. We find that wastewater trends often lead other COVID-19 indicators in predicting new surges.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

An approach for collaborative development of a federated biomedical knowledge graph-based question-answering system: Question-of-the-Month challenges

Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and -related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Impact of Remdesivir Incorporation along the Primer Strand on SARS-CoV-2 RNA-Dependent RNA Polymerase

Remdesivir was the first antiviral drug that received emergency use authorization from the United States Food and Drug Administration and is now formally approved to treat COVID-19. Remdesivir is a nucleotide analogue that targets the RNA-dependent RNA polymerase (RdRp) of coronaviruses, including SARS-CoV-2. The solution of multiple RdRp structures has been one of the main axes of research in the race against the SARS-CoV-2 virus. Several hypotheses of the mechanism of inhibition of RdRp by remdesivir have been proposed, although open questions remain. This work uses molecular dynamics simulations to explore the impact of remdesivir and two analogues as incoming nucleotides and of up to four incorporations of remdesivir along the primer strand on RdRp. The simulation results suggest that the overall structure and the dynamical behavior of RdRp are destabilized by remdesivir and the two analogues in the incoming position. The incorporation of remdesivir along the primer strand impacts specific non-bonded interactions between the nascent RNA and the polymerase subunit, as well as the overall dynamical networks on RdRp. The strongest impact on the structure and dynamics are observed after three incorporations, when remdesivir is located at position -A3, in agreement with previously reported experimental and computational results. Our results provide atomic-level details of the role played by remdesivir on the disruption of RNA synthesis by RdRp and the main drivers of these disruptions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Screening of Therapeutic Agents for COVID-19 Using Machine Learning and Ensemble Docking Studies

The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. In this work, we present an efficient computational strategy that combines machine learning (ML)-based models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host-virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors ( 2 χ n , topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Hydration-Induced Disorder Lowers the Energy Barriers for Methyl Rotation in Drug Molecules

The thermally activated dynamics of methyl groups are important for biochemical activity as they allow for a more efficient sampling of the energy landscape. In this work, we compare methyl rotations in the dry and variously hydrated states of three primary drugs under consideration to treat the recent coronavirus disease (COVID-19), namely, hydroxychloroquine and its sulfate, dexamethasone and its sodium diphosphate, and remdesivir. We find that the main driving force behind the considerable reduction in the activation energy for methyl rotations in the hydrated state is the hydration-induced disorder in the methyl group local environments. Furthermore, the activation energy for methyl rotations in the hydration-induced disordered state is much lower than that in an isolated drug molecule, indicating that neither isolated molecules nor periodic crystalline structures can be used to analyze the potential landscape governing the side group dynamics in drug molecules. Instead, only the explicitly considered disordered structures can provide insight.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Atomic Force Microscopy and Infrared Nanospectroscopy of COVID-19 Spike Protein for the Quantification of Adhesion to Common Surfaces

The COVID-19 pandemic has claimed millions of lives worldwide, sickened many more, and has resulted in severe socio-economic consequences. As society returns to normal, understanding the spread and persistence of SARS CoV-2 on commonplace surfaces can help to mitigate future outbreaks of coronaviruses and other pathogens. We hypothesize that such an understanding can be aided from studying the binding and interaction of viral proteins with non-biological surfaces. Here, we propose a methodology for investigating the adhesion of the SARS CoV-2 spike glycoprotein on common inorganic surfaces such as aluminum-, copper-, iron-, silica-, and ceria-oxides as well as metallic gold. Quantitative adhesion was obtained from the analysis of measured forces at the nanoscale using an atomic force microscope operated under ambient conditions. Without imposing further constraints on the measurement conditions, our preliminary findings suggest that spike glycoproteins interact with similar adhesion forces across the majority of the metal oxides tested with the exception to gold, for which attraction forces ~10 times stronger than all other materials studied were observed. Ferritin, which was used as a reference protein, was found to exhibit similar adhesion forces as SARS CoV-2 spike protein. Further, this study results show that glycoprotein adhesion forces for similar ambient humidity, tip shape, and contact surface are non-specific to the properties of metal oxide surfaces, which are expected to be covered by a thin water film. The findings suggest that at ambient conditions glycoprotein adhesion to metal oxides is primarily controlled by the water capillary forces and they depend on the surface tension of the liquid (water). We discuss further strategies warranted to decipher the intricate nanoscale forces for improved quantification of the adhesion.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

COVID-19: Effects of Environmental Conditions on the Propagation of Respiratory Droplets

As coronavirus disease 2019 (COVID-19) continues to spread, a detailed understanding on the transmission mechanisms is of paramount importance. The disease transmits mainly through respiratory droplets and aerosol. Although models for the evaporation and trajectory of respiratory droplets have been developed, how the environment impacts the transmission of COVID-19 is still unclear. In this study, we investigate the propagation of respiratory droplets and aerosol particles generated by speech under a wide range of temperatures (0–40 °C) and relative humidity (0–92%) conditions. We show that droplets can travel three times farther in low-temperature and high-humidity environment, whereas the number of aerosol particles increases in high-temperature and low-humidity environments. The results also underscore the importance of proper ventilation, as droplets and aerosol spread significantly farther in airstreams. This study contributes to the understanding of the environmental impact on COVID-19 transmission.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Remote Floating-Gate Field-Effect Transistor with 2-Dimensional Reduced Graphene Oxide Sensing Layer for Reliable Detection of SARS-CoV-2 Spike Proteins

Despite intensive research of nanomaterials-based field-effect transistors (FETs) as a rapid diagnostic tool, it remains to be seen for FET sensors to be used for clinical applications due to a lack of stability, reliability, reproducibility, and scalability for mass production. In this work, we propose a remote floating-gate (RFG) FET configuration to eliminate device-to-device variations of two-dimensional reduced graphene oxide (rGO) sensing surfaces and most of the instability at the solution interface. Also, critical mechanistic factors behind the electrochemical instability of rGO such as severe drift and hysteresis were identified through extensive studies on rGO–solution interfaces varied by rGO thickness, coverage, and reduction temperature. rGO surfaces in our RFGFET structure displayed a Nernstian response of 54 mV/pH (from pH 2 to 11) with a 90% yield (9 samples out of total 10), coefficient of variation (CV) < 3%, and a low drift rate of 2%, all of which were calculated from the absolute measurement values. As proof-of-concept, we demonstrated highly reliable, reproducible, and label-free detection of spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a saliva-relevant media with concentrations ranging from 500 fg/mL to 5 μg/mL, with an R 2 value of 0.984 and CV < 3%, and a guaranteed limit of detection at a few pg/mL. Taken together, this new platform may have an immense effect on positioning FET bioelectronics in a clinical setting for detecting SARS-CoV-2.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Light-Induced Transformation of Virus-Like Particles on TiO 2

Titanium dioxide (TiO 2 ) shows significant potential as a self-cleaning material to inactivate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent virus transmission. This study provides insights into the impact of UV-A light on the photocatalytic inactivation of adsorbed SARS-CoV-2 virus-like particles (VLPs) on a TiO 2 surface at the molecular and atomic levels. X-ray photoelectron spectroscopy, combined with density functional theory calculations, reveals that spike proteins can adsorb on TiO 2 predominantly via their amine and amide functional groups in their amino acids blocks. We employ atomic force microscopy and grazing-incidence small-angle X-ray scattering (GISAXS) to investigate the molecular-scale morphological changes during the inactivation of VLPs on TiO 2 under light irradiation. Notably, in situ measurements reveal photoinduced morphological changes of VLPs, resulting in increased particle diameters. These results suggest that the denaturation of structural proteins induced by UV irradiation and oxidation of the virus structure through photocatalytic reactions can take place on the TiO 2 surface. The in situ GISAXS measurements under an N 2 atmosphere reveal that the virus morphology remains intact under UV light. This provides evidence that the presence of both oxygen and UV light is necessary to initiate photocatalytic reactions on the surface and subsequently inactivate the adsorbed viruses. The chemical insights into the virus inactivation process obtained in this study contribute significantly to the development of solid materials for the inactivation of enveloped viruses.

36 MATERIALS SCIENCE↗
DOE OSTI2021

Polymer, Additives, and Processing Effects on N95 Filter Performance

The current severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) pandemic has highlighted the need for personal protective equipment, specifically filtering facepiece respirators like N95 masks. While it is common knowledge that polypropylene (PP) is the industry standard material for filtration media, trial and error is often required to identify suitable commercial precursors for filtration media production. This work aims to identify differences between several commercial grades of PP and demonstrate the development of N95 filtration media with the intent that the industry partners can pivot and help address N95 shortages. Three commercial grades of high melt flow index PP were melt blown at Oak Ridge National Laboratory and broadly characterized by several methods including differential scanning calorimetry (DSC), X-ray diffraction (XRD), and neutron scattering. Despite the apparent similarities (high melt flow and isotacticity) between PP feedstocks, the application of corona charging and charge enhancing additives improve each material to widely varying degrees. From the analysis performed here, the most differentiating factor appears to be related to crystallization of the polymer and the resulting electret formation. Materials with higher crystallization onset temperatures, slower crystallization rates, and larger number of crystallites form a stronger electret and are more effective at filtration.

36 MATERIALS SCIENCE↗
DOE OSTI2023

SARS-CoV-2 M pro Protease Variants of Concern Display Altered Viral Substrate and Cell Host Target Galectin-8 Processing but Retain Sensitivity toward Antivirals

The main protease of SARS-CoV-2 (M pro ) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in M pro may alter the structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOCs) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and the rate of cleavage of a viral peptide. Crystal structures of 11 M pro mutants provided structural insight into their altered functionality. Additionally, we show M pro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and a subsequent significant decrease in cytokine secretion, providing evidence for alterations in the escape of host-antiviral mechanisms. Accordingly, mutations associated with the Gamma VOC and highly virulent Delta VOC resulted in a significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting M pro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗