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At least 883 records · Page 49

Seasonal to Decadal Variability in Focused Groundwater and Contaminant Discharge along a Channelized Stream

Abstract Focused groundwater discharge to streams is problematic at contaminated sites because high fluxes can limit natural attenuation in the hyporheic zone. However, information on location, spatial evolution, and temporal persistence of springs in unlithified sediments over multiyear time scales is limited. We examine discharge at point (~1‐m) to reach (~300‐m) scales along a stream that intercepts trichloroethene and technetium‐99 plumes from a Superfund site. During 2011 to 2012, we seasonally monitored stream and spring flow and contaminant concentrations, along with probing streambed temperatures on a grid in winter and summer, building on prior monitoring during 1999 to 2002. Baseflow measured by both gauging and dye dilution generally increased with distance downstream, and stream and spring discharge varied seasonally, from minima in October to January to maxima in February to June. Thermal anomalies identified by probing occupied approximately 3% to 6% of the reach and typically coincided with visible springs or seeps. Locations of anomalies were similar to those identified in summer 2002, although some orifices disappeared and others emerged. Vertical groundwater fluxes calculated from probing tended to be less than net fluxes calculated from stream discharge, perhaps in part because the assumption of one‐dimensional, steady‐state flow in calculating point fluxes was simplistic. Maximum contaminant concentrations and fluxes decreased between 1999 to 2001 and 2011 to 2012 as a result of partial capture by an upgradient pump‐and‐treat system. Our findings confirm that springs in unlithified sediments can remain stationary within a few meters over decadal time scales, and seasonal variability in discharge can be greater than decadal variability.

Tripathi, Ganesh N.↗

The essential effector SCRE1 in Ustilaginoidea virens suppresses rice immunity via a small peptide region

Summary The biotrophic fungal pathogen Ustilaginoidea virens causes rice false smut, a newly emerging plant disease that has become epidemic worldwide in recent years. The U. virens genome encodes many putative effector proteins that, based on the study of other pathosystems, could play an essential role in fungal virulence. However, few studies have been reported on virulence functions of individual U. virens effectors. Here, we report our identification and characterization of the secreted cysteine‐rich protein SCRE1, which is an essential virulence effector in U. virens . When SCRE1 was heterologously expressed in Magnaporthe oryzae , the protein was secreted and translocated into plant cells during infection. SCRE1 suppresses the immunity‐associated hypersensitive response in the nonhost plant Nicotiana benthamiana . Induced expression of SCRE1 in rice also inhibits pattern‐triggered immunity and enhances disease susceptibility to rice bacterial and fungal pathogens. The immunosuppressive activity is localized to a small peptide region that contains an important ‘cysteine‐proline‐alanine‐arginine‐serine’ motif. Furthermore, the scre1 knockout mutant generated using the CRISPR/Cas9 system is attenuated in U. virens virulence to rice, which is greatly complemented by the full‐length SCRE1 gene. Collectively, this study indicates that the effector SCRE1 is able to inhibit host immunity and is required for full virulence of U. virens .

Zhang, Nan↗

Arabidopsis SnRK1 negatively regulates phenylpropanoid metabolism via Kelch domain-containing F-box proteins

Phenylpropanoid metabolism represents a substantial metabolic sink for the photosynthetically fixed carbon. The evolutionarily conserved Sucrose Non-Fermenting Related Kinase 1 (SnRK1) is a major metabolic sensor that reprograms metabolism upon carbon deprivation. However, it is not clear if and how SnRK1-mediated sugar signaling pathway controls phenylpropanoid metabolism. Here, we show that Arabidopsis SnRK1 negatively regulates phenylpropanoid biosynthesis via a group of Kelch domain-containing F-Box (KFB) proteins that are responsible for the ubiquitination and degradation of phenylalanine ammonia lyase (PAL). Down-regulation of AtSnRK1 significantly promoted the accumulation of soluble phenolics and lignin polymers and drastically increased PAL cellular accumulation but only slightly altered its transcription level. Co-expression of SnRK1α with PAL in Nicotiana benthamiana leaves resulted in the severe attenuation of the latter's protein level, but protein interaction assays suggested PAL is not a direct substrate of SnRK1. Furthermore, up- or down-regulation of AtSnRK1 positively affected KFB PALs gene expression, and energy starvation upregulated KFB PAL expression, which partially depends on AtSnRK1. Collectively, our study reveals that SnRK1 negatively regulates phenylpropanoid biosynthesis, and KFB PALs act as regulatory components of the SnRK1 signaling network, transcriptionally regulated by SnRK1 and subsequently mediating proteasomal degradation of PAL in response to the cellular carbon availability.

59 BASIC BIOLOGICAL SCIENCES↗

OsHUB2 inhibits function of OsTrx1 in heading date in rice

SUMMARY Heading date is one of the most pivotal agronomic traits for rice ( Oryza sativa ) yield and adaptation. Little is known about the crosstalk between histone ubiquitination and histone methylation in rice heading date regulation. Here, we reported HISTONE MONOUBIQUITINATION 1 ( OsHUB1 ) and OsHUB2 are involved in heading date regulation via the Hd1 and Ehd1 pathway. Loss of OsHUB1 and OsHUB2 function resulted in early heading under long‐day and short‐day photoperiods. The expression of Hd3a , RFT1 , and Ehd1 was induced and the transcript levels of Hd1 , Ghd7 , OsCCA1 , OsGI , OsFKF1 , and OsTOC1 were reduced under long‐day conditions, whereas RFT1 and Ehd1 expression was induced in oshub2 mutants under short‐day conditions. OsHUB2 interacted with OsTrx1 and repressed the gene expression of OsTrx1 . OsHUB2 directly bound to Ehd1 to ubiquitinate H2B at Ehd1 , and H2B ubiquitination levels were reduced in oshub2‐2 and oshub2‐3 mutants. OsTrx1 were highly enriched at Ehd1 , and H3K4me3 levels of Ehd1 were upregulated in oshub2‐2 . Mutations of OsTrx1 in the oshub2‐2 background rescued the early‐heading phenotype of oshub2‐2 . The increases in Ehd1 H3K4me3 levels and transcript levels in oshub2‐2 mutants were attenuated in oshub2‐2 ostrx1‐2 double mutants. Together, our results (i) reveal that OsHUB2 represses the function of OsTrx1 and H3K4me3 levels at Ehd1 and (ii) suggest that OsHUB2‐mediated H2B ubiquitination plays critical roles together with H3K4me3 in rice heading date regulation.

Xu, Zuntao↗

Influence of Data Acquisition Algorithms on X-ray Phase Contrast Imaging Computed Tomography

X-ray phase contrast imaging (XPCI) is a non-destructive evaluation technique that enables high-contrast detection of low-attenuation materials that are largely transparent in traditional radiography. Extending a grating based Talbot-Lau XPCI system to three- dimensional imaging with computed tomography (CT) imposes two motion requirements: the analyzer grating must translate transverse to the optical axis to capture image sets for XPCI reconstruction, and the sample must rotate to capture angular data for CT reconstruction. The acquisition algorithm choice determines the order of movement and positioning of the two stages. The choice of image acquisition algorithm for XPCI CT is instrumental to collecting high fidelity data for reconstruction. We investigate how data acquisition influences XPCI CT by comparing two simple data acquisition algorithms and determine that capturing a full phase-stepping image set for a CT projection before rotating the sample results in higher quality data.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

A Systems Approach to Estimating the Uncertainty Limits of X-Ray Radiographic Metrology

Micro- and nanomanufacturing capabilities have rapidly expanded over the past decade to include complex three-dimensional (3D) structure fabrication; however, the metrology required to accurately assess these processes via part inspection and characterization has struggled to keep pace. X-ray computed tomography (CT) is considered an ideal candidate for providing the critically needed metrology on the smallest scales, especially internal features, or inaccessible regions. X-ray CT supporting micro- and nanomanufacturing often push against the poorly understood resolution and variation limits inherent to the machines, which can distort or hide fine structures. In this study, we have developed and experimentally verify a comprehensive analytical uncertainty propagation signal variation flow graph (SVFG) model for X-ray radiography in this work to better understand resolution and image variability limits on the small scale. The SVFG approach captures, quantifies, and predicts variations occurring in the system that limit metrology capabilities, particularly in the micro/nanodomain. This work is the first step to achieving full uncertainty modeling of CT reconstructions and provides insight into improving X-ray attenuation imaging systems. The SVFG methodology framework is applied to generate a complete basis set of functions describing the major sources of variation in radiographs. Five models are identified, covering variation in energy, intensity, length, blur, and position. Radiographic system experiments are defined to measure the parameters required by the SVFGs. Best practices are identified for these measurements. The SVFG models are confirmed via direct measurement of variation to predict variation within 30% on average.

47 OTHER INSTRUMENTATION↗

Attached Jet Velocity Profiles in Mixing Tanks

Free jets have been studied in detail over much of the last century, but the theory for offset and attached jets remains incomplete. Attached jets differ from free jets in that they lose momentum to nearby surfaces, attenuating their velocities. The velocity profiles of free circular jets are nearly Gaussian, with quantitative mathematical descriptions derived from first principles by Goertler and Tollmien (Rajaratnam, 1976). In contrast, mathematical descriptions of three-dimensional attached jets from circular nozzles remain much less mature. Agelin-Chaab and Tachie (2011) used particle imaging velocimetry of a three-dimensional attached jet to show that the scaled velocity decays with scaled distance from the nozzle with a power law exponent between -1.15 and -1.21, which is larger in magnitude than that of a free jet. However, quantitative analytical expressions for the velocity profiles of attached jets similar to those of free jets remain elusive. This paper addresses this critical gap. Here we evaluate the velocity profiles of three-dimensional offset jets emerging from circular nozzles that that become attached jets. These jets lose momentum due to interactions with nearby surfaces and are important to evaluating flows in mixing vessels and to suspending solids and trapped gases in radioactive waste tanks. Despite the importance of attached jets, prior insight has been purely experimental, limited to overly simplistic analytical models, or restricted to computationally expensive computational fluid dynamics case studies. We compare the expression of Verhoff (1963) to experimental results to find reasonable quantitative agreement. As stated by Agelin-Chaab and Tachie (2011), “detailed velocity measurements of 3D offset jets are rare.” Such remains the case. This study adds to the literature by providing information at two additional Reynolds numbers (1.43 106 and 1.87 106) and evaluating simple but accurate expressions for velocity profiles. These Reynolds numbers are an order of magnitude higher than prior reports. The semi-empirical stream wise velocity profile perpendicular to the surface proposed by Verhoff (1963) is in approximate agreement with these velocity profiles, which is surprising because these attached jets are three-dimensional instead of two-dimensional as evaluated by Verhoff. However, additional work is necessary to fully describe these profiles quantitatively.

jet, attached jet, offset jet↗

effect of ambient pressure on the behavior of single-component fuels in a gasoline multi-hole injector

The injection characteristics of neat ethanol and pure isooctane are studied under different ambient pressure and temperature conditions. Injection underflash-boiling conditions can enhance liquid atomization and evaporation, providing the possibility of improvement in the fuel/air mixing. These superheated conditions often introduce phenomena that are not taken into account in the standard modeling of sprays for engine applications. The present work proposes a numerical investigation of the behavior of Engine Combustion Network's 8-hole spray-G injector, starting at the subcooled nominal condition and reducing the ambient pressure at constant low temperature to reach the flare flash-boiling condition. To initialize the properties of the injected fuel, the flow in the nozzle is simulated with a Eulerian approach, handling the two phases with a mixture model and the phase change, due to cavitation and flash boiling, with the Homogenous Relaxation Model. A map of the mixture's kinematic and thermal behavior is obtained at the interface between the injector and the chamber to initialize the Lagrangian simulations. A literature-based vaporization model is implemented to obtain the proper description of the characteristic features of a multi-hole spray under super-heated conditions, like plume-plume interaction. The numerical representation of the spray is validated in terms of penetration and radial spreading on DBI images, reproducing the light attenuation profiles caused by the presence of the liquid spray. Simulations show that coupled nozzle flow and spray calculations capture the spray morphology and shape better compared to calculations performed without considering the nozzle flow simulation details, especially under flare flash conditions.

Nocivelli, Lorenzo↗

Evaluation of Common Thermoplastic Polymers in High-Pressure Cycling Hydrogen Under Ambient and Cold Environments as Applicable to the Hydrogen Infrastructure

Thermoplastic polymers are required to perform unfailingly under stringent conditions of changing pressures (35 MPa to 70 MPa) and temperatures (-40°C to +85°C) in storage and fueling operations. Although diffusivity in glassy polymers appear to be an order of magnitude lower than elastomers, polymer microstructural attributes such as degree of crystallinity and presence of polar and non-polar groups on the main chain with and without branching can play a substantial role in influencing their behaviors in hydrogen environments. In the work described here, the effect of high-pressure hydrogen cycling on PEEK, PTFE, PA11, HDPE, POM (and different commercial grades of these polymers) under ambient and cold (-40°C) conditions is addressed. Ex-situ characterization for polymer changes included density measurements for impact of hydrogen retention, hardness changes using nanoindentation, storage modulus and glass transition changes using dynamic mechanical and thermal analysis (DMTA), degree of crystallization with Differential Scanning Calorimetry (DSC) and tensile testing following ASTM D412. In other evaluations, solid-state nuclear magnetic resonance (NMR), attenuated total reflectance Fourier transform infra-red spectroscopy (ATRFTIR), X-ray diffraction (XRD), and X-ray CT results are presented. The overall impact of these evaluations is to establish a technical basis for the behaviors of common thermoplastics in cycling hydrogen environments under ambient and cold temperatures while establishing the relationship between polymer structure-based properties and hydrogen transport effects.

Menon, Nalini C.↗

Feasibility of Lead Fast Reactor Heat Exchanger Tube Online Monitoring

Within virtually all reactor systems with heat exchangers, the thinnest barriers between primary and secondary fluids are the heat exchanger tubes. Consistent with light water reactor experience, the advanced reactor heat exchangers are the most susceptible regions for corrosion and leakage (NRC, 2019). Moreover, traditional inspections and repairs using robotics will be expensive or impractical. On-line structural health corrosion monitoring (OLSHM) is therefore desirable to detect tube degradation prior to leaks that may allow mixing of heat exchanger fluids. Rhetorically many molten salt reactor (MSR) designers plan for on-line monitoring of critical reactor components including heat exchangers but there are no proven OLSHM sensors or systems for MSR heat exchangers. Guided wave ultrasound from the tube-end or ID using conventional low-temperature piezoelectric sensors has been shown to be sensitive to pits and cracks less than 50% through-wall in long pipes and tubes (Narayanan M.M., 2019) . Mode and frequency selection are important for practical sensor design decisions and ultimate performance. The L-0 wave-mode is easily excited by L-mode transducers but they have surface normal wave motion that will be sensitive to and more attenuative because of fluid interaction with the tube surface (Rose J.L., 1994). Shear Horizontal (SH) wave modes have material motion parallel to the tube surface therefore are virtually unaffected by fluid interaction. For SH-0 to be nondispersive in steel, the frequency-thickness product (MHz-mm) must be less than approximately 1.5. SH mode transducers must be coupled by a material that can support shear stress; a thin layer of honey works well for temporary sensors and an adhesive or a brazed metallurgical bond for permanent sensors. If sensors are incorporated into the fabrication process, the same kinds of SH-0 waves can be generated from the stagnant flow area of the tube OD without compromising the heat-exchange tube function. Piezoelectric materials are also available that can withstand harsh temperatures of molten salt heat exchangers (Stevenson T., 2015) (Machura et al., 2008). Though they may not have as high-performance characteristics, their performance only needs to be good enough to detect flaws of interest. This project attempts to demonstrate feasibility to develop a sensor that can be sensitive to flaws of interest and perform long-term monitoring of a molten salt reactor heat exchanger. Benefits to the advanced reactor system include: • Minimizing the expense of a reactor shut down for periodic inspection—only shutdown for cause. • Reduce risk of unexpected tube rupture by detecting flaws before they grow to through-wall leaks. • Cost reduction by minimizing need to design for manual/robotic inspectability. Transducer design, characterization of the beam profile, wedges vs. direct application of piezoelectric sensors, and ultrasonic pulse-echo responses from a representative heat exchange tube with fabricated flaw types are discussed.

On-Line Tube Monitor, Guided Wave Ultrasound, SH-0↗

Picometer sensitivity metrology for EUV absorber phase

With growing interest in EUV attenuated phase-shift masks due to their superior image quality for applications such as dense contact and pillar arrays, it is becoming critical to model, measure, and monitor the intensity and relative phase of multilayer and absorber reflections. We present a solution based on physical modeling of reflectometry data, which can achieve single picometer phase precision and sensitivity to changes in average film thickness below one atomic monolayer. We measure absorber and multilayer reflectivity to determine thin-film parameters with a multidimensional optimization and then acquire a new measurement of either multilayer or absorber to determine perturbations in surface contamination thickness. While it is difficult to assess the accuracy of the first step, the simplicity of the second step allows us to characterize our sensitivity to changes in contamination thickness. Thus, we apply this analysis using an initial set of measurements and repeated measurements after a period of storage. For the multilayer, the total contamination growth was 1068 pm, which occurred almost exclusively during storage (1085 pm) and decreased very slightly during repeated measurements (-17 pm). For the absorber, the behavior was quite different, with a total growth of 126 pm, which occurred much less during storage (28 pm) and primarily during repeated measurements (98 pm). Ultimately, the change in relative phase (absorber minus multilayer) was -0.86 deg for the multilayer and -1.12 deg for the absorber. We estimate the precision of the surface contamination measurement to be 3σ < 6 pm for measuring thickness and 3σ < 0.2 deg for measuring phase.

36 MATERIALS SCIENCE↗

Development of polarization-sensitive optical coherence tomography imaging platform and metrics to quantify electrostimulation-induced peripheral nerve injury in vivo in a small animal model

Neuromodulation devices are rapidly evolving for the treatment of neurological diseases and conditions. Injury from implantation or long-term use without obvious functional losses is often only detectable through terminal histology. New technologies are needed that assess the peripheral nervous system (PNS) under normal and diseased or injured conditions. We aim to demonstrate an imaging and stimulation platform that can elucidate the biological mechanisms and impacts of neurostimulation in the PNS and apply it to the sciatic nerve to extract imaging metrics indicating electrical overstimulation. A sciatic nerve injury model in a 15-rat cohort was observed using a newly developed imaging and stimulation platform that can detect electrical overstimulation effects with polarization-sensitive optical coherence tomography. The sciatic nerve was electrically stimulated using a custom-developed nerve holder with embedded electrodes for 1 h, followed by a 1-h recovery period, delivered at above-threshold Shannon model k-values in experimental groups: sham control (SC, n = 5, 0.0 mA / 0 Hz), stimulation level 1 (SL1, n = 5, 3.4 mA / 50 Hz, and k = 2.57), and stimulation level 2 (SL2, n = 5, 6.8 mA / 100 Hz, and k = 3.17). The stimulation and imaging system successfully captured study data across the cohort. When compared to a SC after a 1-week recovery, the fascicle closest to the stimulation lead showed an average change of +4 % / – 309 % (SL1/SL2) in phase retardation and –79 % / – 148 % in optical attenuation relative to SC. Analysis of immunohistochemistry (IHC) shows a +1 % / – 36 % difference in myelin pixel counts and –13 % / + 29 % difference in axon pixel counts, and an overall increase in cell nuclei pixel count of +20 % / + 35 % . These metrics were consistent with IHC and hematoxylin/eosin tissue section analysis. The poststimulation changes observed in our study are manifestations of nerve injury and repair, specifically degeneration and angiogenesis. Optical imaging metrics quantify these processes and may help evaluate the safety and efficacy of neuromodulation devices.

60 APPLIED LIFE SCIENCES↗

Calibration, modeling, parameterization, and verification of the instrument transfer function of an interferometric microscope

Interferometric microscopes are used to measure surface roughness, from which the computed power spectral density function can be used to extract bandwidth-limited values of the various surface properties, such as root-mean-square (rms) height and slope errors. Measurements with a microscope equipped with different objectives that have an overlapping spatial frequency range usually give different rms results over the common frequency bandwidth. This is a result of different instrument transfer functions (ITFs) that attenuate spatial frequencies by different amounts over the overlapping range. We report on the use of binary pseudo-random array (BPRA) standards to characterize the ITF of an interferometric microscope with the various objectives. We use a simple model of a 1D binary Results show that the spectrum for an undersampled array is a cosine function, rather than a straight line, constant white noise spectrum. We have an analytical model of the ITF that includes the effects of an obscured aperture and defocus, in addition to the usual parameters of numerical aperture, wavelength, and sampling period. In addition, the model includes the effect of aliasing of spatial frequency components beyond the Nyquist back into the sub-Nyquist region. We compare the model PSD predictions to the measurements performed with different objectives. Departures of the measured PSDs from the model predictions indicate that there are higher-order ITF corrections yet to be identified and included in the model.

Takacs, PZ↗

Ultra-Long Distance BOTDA Sensor System Employing Hybrid Amplification and Advanced Noise Reduction Techniques

Brillouin Optical Time Domain Analysis (BOTDA) sensor system play a pivotal role in distributed sensing, which enables precise measurements of strain and temperature across extensive fiber lengths. Nonetheless, challenges emerge as distances grow due to signal attenuation and noise interference resulting in measurement errors. This research offers a comprehensive strategy to extend the sensing range of BOTDA systems beyond 10’s of kilometers while maintaining high spatial resolutions. Such enhanced sensing is realized through the integration of distributed Raman amplification, inline amplification using erbium-doped fiber amplifiers (EDFA), and advanced noise reduction techniques. Leveraging inherent redundancy in measured data as a function of frequency and fiber distance, the non-local means (NLM) filter removes noise while preserving essential physical information. This approach proves particularly advantageous in BOTDA systems, where accurate measurement of Brillouin scattering signals is paramount for long-range sensing, while concurrently safeguarding high spatial resolutions. In summary, this research has shown a holistic exploration of extending BOTDA's distance sensing capabilities up to 150 km with spatial resolutions of 8 meters.

Bhatta, Hari↗

Closed-form existence conditions for bandgap resonances in a finite periodic chain under general boundary conditions

Bragg scattering in periodic media generates bandgaps, frequency bands where waves attenuate rather than propagate. Yet, a finite periodic structure may exhibit resonance frequencies within these bandgaps. This is caused by boundary effects introduced by the truncation of the nominal infinite medium. Previous studies of discrete systems determined existence conditions for bandgap resonances, although the focus has been limited to mainly periodic chains with free–free boundaries. In this paper, we present closed-form existence conditions for bandgap resonances in discrete diatomic chains with general boundary conditions (free–free, free–fixed, fixed–free, or fixed–fixed), odd or even chain parity (contrasting or identical masses at the ends), and the possibility of attaching a unique component (mass and/or spring) at one or both ends. The derived conditions are consistent with those theoretically presented or experimentally observed in prior studies of structures that can be modeled as linear discrete diatomic chains with free–free boundary conditions. An intriguing case is a free–free chain with even parity and an arbitrary additional mass at one end of the chain. Introducing such an arbitrary mass underscores a transition among a set of distinct existence conditions, depending on the type of chain boundaries and parity. The proposed analysis is applicable to linear periodic chains in the form of lumped-parameter models, examined across the frequency spectrum, as well as continuous granular media models, or similar configurations, examined in the low-frequency regime.

Bastawrous, Mary V.↗

Time reversal in a phononic crystal using finite-element modeling and an equivalent circuit model

A phononic crystal acts as a dispersive medium with a phase speed that is lower than the bulk wave speed at frequencies below the resonance of a single resonator. Time reversal is used to compensate for the phase shifts caused by individual resonators as the waves enter the medium and enable focusing of acoustic waves among the crystal. An equivalent circuit, which can predict the dispersion and attenuation of the crystal model, is shown and compared to a full-wave finite-element simulation in frequency and time. The phase shift due to a single resonator is also depicted.

Kingsley, Adam D. (ORCID:0000000226611788)↗

Performance of three hydrophone flow shields in a tidal channel

Pseudosound caused by turbulent pressure fluctuations in fluid flow past a hydrophone, referred to as flow noise, can mask propagating sounds of interest. Flow shields can mitigate flow noise by reducing non-acoustic pressure fluctuations sensed by a hydrophone. We evaluate the performance of three hydrophone flow shields (two nylon fabrics and an oil-filled enclosure) in a tidal channel with peak current speed of 1.3 m s−1. All three flow shields reduced flow noise without attenuating propagating sound below 20 kHz. The oil-filled enclosure performed best, reducing flow noise by over 30 dB at frequencies below 40 Hz.

47 OTHER INSTRUMENTATION↗

Toward wide-spectrum antivirals against coronaviruses: Molecular characterization of SARS-CoV-2 NSP13 helicase inhibitors

To date, effective therapeutic treatments that confer strong attenuation against coronaviruses (CoVs) remain elusive. Among potential drug targets, the helicase of CoVs is attractive due to its sequence conservation and indispensability. We rely on atomistic molecular dynamics simulations to explore the structural coordination and dynamics associated with the SARS-CoV-2 Nsp13 apo enzyme, as well as their complexes with natural ligands. A complex communication network is revealed among the five domains of Nsp13, which is differentially activated because of the presence of the ligands, as shown by shear strain analysis, principal components analysis, dynamical cross-correlation matrix analysis, and water transport analysis. The binding free energy and the corresponding mechanism of action are presented for three small molecules that were shown to be efficient inhibitors of the previous SARS-CoV Nsp13 enzyme. Together, our findings provide critical fresh insights for rational design of broad-spectrum antivirals against CoVs.

59 BASIC BIOLOGICAL SCIENCES↗