Integrated System for On-Site Rapid and Safe Screening of COVID-19.

Since the outbreak of coronavirus disease 2019 (COVID-19), the epidemic has been spreading around the world for more than 2 years. Rapid, safe, and on-site detection methods of COVID-19 are in urgent demand for the control of the epidemic. Here, we established an integrated system, which incorporates a machine-learning-based Fourier transform infrared spectroscopy technique for rapid COVID-19 screening and air-plasma-based disinfection modules to prevent potential secondary infections. A partial least-squares discrimination analysis and a convolutional neural network model were built using the collected infrared spectral dataset containing 857 training serum samples. Furthermore, the sensitivity, specificity, and prediction accuracy could all reach over 94% from the results of the field test regarding 968 blind testing samples. Additionally, the disinfection modules achieved an inactivation efficiency of 99.9% for surface and airborne tested bacteria. The proposed system is conducive and promising for point-of-care and on-site COVID-19 screening in the mass population.

Study on flexible surface dielectric barrier discharge plasma film for in situ inactivation of bacteria and viruses

COVID-19 is still pandemic in the world although it has lasted for more than two years, in situ real-time disinfection of curved surfaces in public places is extremely urgent. A flexible plasma film based on surface dielectric barrier discharge is proposed in this study. In situ disinfection effect and the influence of curvature on the performance are studied. The results showed that the film could in situ inactivate a variety of pathogens. Specifically, 10 min plasma treatment results in a log reduction of 3.10, 3.42, and 3.03 for Escherichia coli, Staphylococcus aureus, and vesicular stomatitis virus, respectively. The discharge power and disinfection effect of the film are independent of the curvature, which proves that it can be used for in situ disinfection of curved surfaces. It is speculated that the combined effects of a strong electric field and radical etching physical damage as well as the chemical damage of reactive oxygen and nitrogen species to the protein are the main reasons for the inactivation of pathogens. The inhibition of the film to Omicron type SARS-CoV-2 pseudovirus is 99.3%, and the killing rate to natural bacteria is 94.3%. The film can run for at least 10 h without significant reduction in disinfection effect. In addition, large-scale and digitalization increase the practical potential of a disinfection film. In conclusion, this film is expected to realize in situ real-time disinfection of curved surfaces such as the buttons of the elevator or instrument and door handles, which is of great significance in blocking the spread of COVID-19. [ FROM AUTHOR] Copyright of Applied Physics Letters is the property of American Institute of Physics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

In-duct grating-like dielectric barrier discharge system for air disinfection.

In the context of spreading Coronavirus disease 2019 (COVID-19), the combination of heating, ventilation, and air-conditioning (HVAC) system with air disinfection device is an effective way to reduce transmissible infections. Atmospheric-pressure non-equilibrium plasma is an emerging technique for fast pathogen aerosol abatement. In this work, in-duct disinfectors based on grating-like dielectric barrier discharge (DBD) plasmas with varied electrode arrangements were established and evaluated. The highest airborne bacterial inactivation efficiency was achieved by 'vertical' structure, namely when aerosol was in direct contact with the discharge region, at a given discharge power. For all reactors, the efficiency was linearly correlated to the discharge power (R2 =0.929-0.994). The effects of environmental factors were examined. Decreased airflow rates boosted the efficiency, which reached 99.8% at the velocity of 0.5 m/s with an aerosol residence time of ~3.6 ms. Increasing humidity (relative humidity (RH)=20-60%) contributed to inactivation efficacy, while high humidity (RH=70%-90%) led to a saturated efficiency, possibly due to the disruption of discharge uniformity. As suggested by the plasma effluent treatment and scavenger experiments, gaseous short-lived chemical species or charged particles were concluded as the major agents accounting for bacterial inactivation. This research provides new hints for air disinfection by DBD plasmas.

Investigating interactions between chloroquine/hydroxychloroquine and their single enantiomers and angiotensin-converting enzyme 2 by a cell membrane chromatography method.

Chloroquine and hydroxychloroquine have been studied since the early clinical treatment of SARS-CoV-2 outbreak. Considering these two chiral drugs are currently in use as the racemate, high-expression angiotensin-converting enzyme 2 cell membrane chromatography was established for investigating the differences of two paired enantiomers binding to angiotensin-converting enzyme 2 receptor. Molecular docking assay and detection of SARS-CoV-2 spike pseudotyped virus entry into angiotensin-converting enzyme 2-HEK293T cells were also conducted for further investigation. Results showed that each single enantiomer could bind well to angiotensin-converting enzyme 2, but there were differences between the paired enantiomers and corresponding racemate in frontal analysis. R-Chloroquine showed better angiotensin-converting enzyme 2 receptor binding ability compared to S-chloroquine/chloroquine (racemate). S-Hydroxychloroquine showed better angiotensin-converting enzyme 2 receptor binding ability than R-hydroxychloroquine/hydroxychloroquine. Moreover, each single enantiomer was proved effective compared with the control group; compared with S-chloroquine or the racemate, R-chloroquine showed better inhibitory effects at the same concentration. As for hydroxychloroquine, R-hydroxychloroquine showed better inhibitory effects than S-hydroxychloroquine, but it slightly worse than the racemate. In conclusion, R-chloroquine showed better angiotensin-converting enzyme 2 receptor binding ability and inhibitory effects compared to S-chloroquine/chloroquine (racemate). S-Hydroxychloroquine showed better angiotensin-converting enzyme 2 receptor binding ability than R-hydroxychloroquine/hydroxychloroquine (racemate), while the effect of preventing SARS-CoV-2 pseudovirus from entering cells was weaker than R-hydroxychloroquine/hydroxychloroquine (racemate).

Disinfection of Escherichia coli in ice by surface dielectric barrier discharge plasma.

A variety of pathogens can cause people to suffer from serious diseases, and the transmission of COVID-19 through the cold chain has once again attracted people's attention to cold chain disinfection. Unfortunately, there is no mature cold chain disinfection technique yet. In this study, a low-temperature plasma disinfection technique for a cold chain is proposed. The disinfection effect of plasma generated by surface dielectric barrier discharge on Escherichia coli in ice at cryogenic temperature is studied, and the possible disinfection mechanism is discussed. It is found that the O3 mode and the NOx mode also exist in the surface dielectric barrier discharge at cryogenic temperature, just as at room temperature. The disinfection effect of both modes is weak in 5 min plasma treatment, but in 60 min post-treatment, the NOx mode shows a stronger disinfection effect, with 4.45 log reduction. It is speculated that gaseous H2O2 and NOx can be adsorbed on the ice surface in the NOx mode and then converted into peroxynitrite, which is a powerful bactericidal species. In conclusion, a low-temperature plasma is a promising technique for cold chain disinfection, which is of great significance for ensuring people's health.

Oroxylin A is a severe acute respiratory syndrome coronavirus 2-spiked pseudotyped virus blocker obtained from Radix Scutellariae using angiotensin-converting enzyme II/cell membrane chromatography.

The current worldwide outbreak of the coronavirus disease 2019 (COVID-19) has been declared a public health emergency. The angiotensin-converting enzyme II (ACE2) has been reported as the primary host-cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of COVID-19. In this study, we screened ACE2 ligands from Radix Scutellariae and investigated its suppressive effect on SARS-CoV-2 spiked pseudotyped virus in vitro. HEK293T cells stably expressing ACE2 receptors (ACE2 cells) were used to provide the receptor for the ACE2/cell membrane chromatography (CMC) method used for analysis. The SARS-CoV-2-spiked pseudotyped virus was used to examine the anti-viropexis effect of the screened compounds in ACE2 cells. Molecular docking and the surface plasmon resonance (SPR) assay were used to determine the binding properties. Oroxylin A exhibited an appreciable suppressive effect against the entrance of the SARS-CoV-2-spiked pseudotyped virus into ACE2 cells, which showed good binding to ACE2 as determined using SPR and CMC. Oroxylin A was shown to be a potential candidate in the treatment for COVID-19 by virtue of its blocking the entrance of SARS-CoV-2 into ACE2 cells by specifically binding to the ACE2 receptor.

Fast Screening and Primary Diagnosis of COVID-19 by ATR-FT-IR.

The outbreak of coronavirus disease 2019 (COVID-19) has led to substantial infections and mortality around the world. Fast screening and diagnosis are thus crucial for quick isolation and clinical intervention. In this work, we showed that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR) can be a primary diagnostic tool for COVID-19 as a supplement to in-use techniques. It requires only a small volume (∼3 µL) of the serum sample and a shorter detection time (several minutes). The distinct spectral differences and the separability between normal control and COVID-19 were investigated using multivariate and statistical analysis. Results showed that ATR-FT-IR coupled with partial least squares discriminant analysis was effective to differentiate COVID-19 from normal controls and some common respiratory viral infections or inflammation, with the area under the receiver operating characteristic curve (AUROC) of 0.9561 (95% CI: 0.9071-0.9774). Several serum constituents including, but not just, antibodies and serum phospholipids could be reflected on the infrared spectra, serving as "chemical fingerprints" and accounting for good model performances.

Cell membrane chromatography for the analysis of the interaction between chloroquine and hydroxychloroquine with ACE2 receptors.

The recent emergence of the novel pathogenic coronavirus disease 2019 (COVID-19) is responsible for a worldwide pandemic. In sight of this, there has been growing interest in the use of chloroquine (CQ) and hydroxychloroquine (HCQ) as potential treatments. In this study, we use angiotensin converting enzyme 2 (ACE2) over-expressed cell membrane chromatography (CMC) to study the interaction of CQ and HCQ with ACE2 receptor. Both CQ and HCQ were retained on the ACE2/CMC column. Then we analyzed the binding character of CQ and HCQ to ACE2 by CMC frontal analysis, ionic force investigation and competitive binding experiment. Results showed that CQ and HCQ KD values obtained from the CMC frontal analysis method were 8.22(±0.61) × 10-7 M and 11.70(±2.44) × 10-7 M. Compare to CQ, HCQ has the weaker affinity with ACE2. The action force of CQ, HCQ and ACE2 is mainly ionic force. CQ and HCQ have different degrees of competitive binding relationship with ACE2. Our study revealed the interaction of CQ and HCQ with ACE2 receptor, which provides new insights for the use of CQ and HCQ in the treatment of COVID-19. Moreover, this biomimetic drug screening method is expected to open the door for rapid targeting and separating bioactive ingredients active towards ACE2 receptor.

Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus.

BACKGROUND: The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating . The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. PURPOSE: The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. METHODS: In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. RESULTS: Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD = (7.31 ± 0.62)e-7 M and (4.82 ± 0.87)e-7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. CONCLUSIONS: CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection.