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1.
Head Neck ; 45(8): 1979-1985, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-20233770

ABSTRACT

BACKGROUND: To evaluate the impact of coronavirus disease 2019 (COVID-19) pandemic on disease extent in patients with nasopharyngeal carcinoma (NPC) using 18 fuorodeoxyglucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: This retrospective cohort study included biopsy-proven, newly diagnosed NPC patients using whole-body FDG PET/MR staging in two selected intervals: 1 May 2017 to 31 January 2020 (Group A, the pre-COVID-19 period), and 1 February 2020 to 30 June 2021 (Group B, the COVID-19 period). RESULTS: Three-hundred and ninety patients were included. No significant difference was observed in terms of T classification, N classification, overall stage, N stations, and M stations between the two groups (p > 0.05). For the involved neck node levels, more patients had developed level Vc metastasis in the group B (p = 0.044). CONCLUSION: Although the overall stage was not affected, more patients with NPC had developed level Vc metastasis in the era of COVID-19.


Subject(s)
COVID-19 , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/diagnostic imaging , Nasopharyngeal Carcinoma/pathology , Fluorodeoxyglucose F18 , Pandemics , Retrospective Studies , Nasopharyngeal Neoplasms/pathology , Tomography, X-Ray Computed/methods , Neoplasm Staging , Positron-Emission Tomography/methods , Magnetic Resonance Imaging , Radiopharmaceuticals
2.
Signal Transduct Target Ther ; 8(1): 242, 2023 Jun 10.
Article in English | MEDLINE | ID: covidwho-20241193

ABSTRACT

Repurposing existing drugs to inhibit SARS-CoV-2 infection in airway epithelial cells (AECs) is a quick way to find novel treatments for COVID-19. Computational screening has found dicoumarol (DCM), a natural anticoagulant, to be a potential SARS-CoV-2 inhibitor, but its inhibitory effects and possible working mechanisms remain unknown. Using air-liquid interface culture of primary human AECs, we demonstrated that DCM has potent antiviral activity against the infection of multiple Omicron variants (including BA.1, BQ.1 and XBB.1). Time-of-addition and drug withdrawal assays revealed that early treatment (continuously incubated after viral absorption) of DCM could markedly inhibit Omicron replication in AECs, but DCM did not affect the absorption, exocytosis and spread of viruses or directly eliminate viruses. Mechanistically, we performed single-cell sequencing analysis (a database of 77,969 cells from different airway locations from 10 healthy volunteers) and immunofluorescence staining, and showed that the expression of NAD(P)H quinone oxidoreductase 1 (NQO1), one of the known DCM targets, was predominantly localised in ciliated AECs. We further found that the NQO1 expression level was positively correlated with both the disease severity of COVID-19 patients and virus copy levels in cultured AECs. In addition, DCM treatment downregulated NQO1 expression and disrupted signalling pathways associated with SARS-CoV-2 disease outcomes (e.g., Endocytosis and COVID-19 signalling pathways) in cultured AECs. Collectively, we demonstrated that DCM is an effective post-exposure prophylactic for SARS-CoV-2 infection in the human AECs, and these findings could help physicians formulate novel treatment strategies for COVID-19.


Subject(s)
COVID-19 , Dicumarol , Humans , SARS-CoV-2 , COVID-19/genetics , Epithelium
3.
Nat Commun ; 14(1): 2800, 2023 05 16.
Article in English | MEDLINE | ID: covidwho-2326577

ABSTRACT

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.


Subject(s)
COVID-19 , Animals , Cricetinae , Humans , Male , Phylogeny , SARS-CoV-2/genetics , Recombination, Genetic , Spike Glycoprotein, Coronavirus/genetics
4.
Chinese Journal of Digestive Surgery ; 21(11):355-362, 2022.
Article in Chinese | CAB Abstracts | ID: covidwho-2320860

ABSTRACT

Objective: To investigate the effect of perioperative oral nutritional supplementation on the short-term curative effect of obese patients after laparoscopic sleeve gastrectomy (LSG). Methods: A prospective research method was adopted. The clinical data of 218 obese patients who underwent LSG in Ningxia Medical University General Hospital from January 2018 to December 2021 were selected. The patients who received oral nutritional supplement therapy during the perioperative period were set as the experimental group, and those who received conventional treatment were set as the control group. Observation indicators: (1) Grouping of enrolled patients. (2) Postoperative and follow-up situation. (3) Nutrition-related indicators. (4) Diet compliance. (5) Status of weight loss-related indicators. Follow-up visits were conducted by telephone, We Chat and outpatient visits. The patients were followed up once 30 days after discharge, including albumin (Alb), hemoglobin (Hb), dietary compliance and weight loss-related indicators. The follow-up time will end in February 2022. The measurement data with normal distribution were expressed as x+or-s, and the comparison between groups was performed by independent sample t test. The measurement data is represented by M (range), and the comparison between groups is performed by Mann?Whitney U test. Enumeration data were expressed as absolute numbers or percentages, and the X2 test was used for comparison between groups. Repeated measures data were analyzed by repeated measures analysis of variance. The rank sum test was used to compare the rank data. Results (1) Grouping of the enrolled patients. Screened 218 eligible patients;42 males and 176 females;age (32+or-9) years;body mass index (BMI) (39+or-7) kg/m2. Among the 218 patients, there were 109 cases in the test group and 109 cases in the control group. Gender (male, female), age, BMI, preoperative Alb, and preoperative Hb of patients in the test group were 17 and 92 cases, (33+or-9) years old, (39+or-7) kg/m2, (40.6+or-4.8) g /L, (141.7+or-13.9) g/L;the above indicators in the control group were 25 and 84 cases, (31+or-8) years old, (39+or-8) kg/m2, (40.9+or-4.2) g/L, (142.9+or-9.7) g/L;there was no significant difference in the above (X2=1.89, t=-1.52, 0.51, 0.40, 0.71, P > 0.05). (2) Postoperative and follow-up situation. The first hospitalization time and first hospitalization expenses of the patients in the experimental group were (9.1+or-2.9) d and (3.6+or-0.5) ten thousand yuan respectively;the above indicators of the patients in the control group were (4.9+or-1.0) ten thousand yuan respectively;There were statistically significant differences in the above indicators between the two groups (t=5.58, 12.38, P < 0.05). Among the 218 patients, 119 were followed up, including 62 in the experimental group and 57 in the control group. The 119 patients were followed up for 31.0 (25.0-38.0) days. Among the 218 patients, 14 cases had postoperative complications and led to rehospitalization, including 2 cases in the experimental group, 1 case of nausea and vomiting and 1 case of intestinal obstruction;12 cases in the control group, 10 cases of nausea and vomiting, gastric fistula 2 cases;there was a statistically significant difference between the two groups in hospital readmission (X2=7.63, P < 0.05). The time interval between re-admission and first discharge of 14 patients was (22.0+or-6.7) days. (3) Nutrition-related indicators. The Alb and Hb levels of 62 patients in the experimental group who were followed up before operation, before the first discharge, and 1 month after operation were (40.4+or-5.5) g/L, (35.9+or-3.8) g/L, (45.4+or-2.9) g/L, respectively and (140.8+or-13.9) g/L, (130.5+or-16.9) g/L, (147.8+or-17.2) g/L;the above indicators of 57 patients in the control group were (41.2+or-3.9) g/L, (34.2 +or-3.9) g/L, (42.7+or-5.3) g/L and (143.0+or-9.7) g/L, (122.9+or-12.8) g/L, (139.0+or-11.4) g/L;There was a statistically significant difference between the Alb and Hb groups from preoperative to postoperative 1 mont

5.
Adv Healthc Mater ; : e2300673, 2023 May 03.
Article in English | MEDLINE | ID: covidwho-2320621

ABSTRACT

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.

6.
ACS Cent Sci ; 9(5): 1046-1058, 2023 May 24.
Article in English | MEDLINE | ID: covidwho-2320579

ABSTRACT

Neutralizing antibodies and fusion inhibitory peptides have the potential required to combat the global pandemic caused by SARS-CoV-2 and its variants. However, the lack of oral bioavailability and enzymatic susceptibility limited their application, necessitating the development of novel pan-CoV fusion inhibitors. Herein we report a series of helical peptidomimetics, d-sulfonyl-γ-AApeptides, which effectively mimic the key residues of heptad repeat 2 and interact with heptad repeat 1 in the SARS-CoV-2 S2 subunit, resulting in inhibiting SARS-CoV-2 spike protein-mediated fusion between virus and cell membranes. The leads also displayed broad-spectrum inhibitory activity against a panel of other human CoVs and showed strong potency in vitro and in vivo. Meanwhile, they also demonstrated complete resistance to proteolytic enzymes or human sera and exhibited extremely long half-life in vivo and highly promising oral bioavailability, delineating their potential as pan-CoV fusion inhibitors with the potential to combat SARS-CoV-2 and its variants.

7.
Microb Cell Fact ; 22(1): 97, 2023 May 10.
Article in English | MEDLINE | ID: covidwho-2316790

ABSTRACT

The filamentous fungus Trichoderma reesei (teleomorph Hypocrea jecorina, Ascomycota) is a well-known lignocellulolytic enzymes-producing strain in industry. To increase the fermentation titer of lignocellulolytic enzymes, random mutagenesis and rational genetic engineering in T. reesei were carried out since it was initially found in the Solomon Islands during the Second World War. Especially the continuous exploration of the underlying regulatory network during (hemi)cellulase gene expression in the post-genome era provided various strategies to develop an efficient fungal cell factory for these enzymes' production. Meanwhile, T. reesei emerges competitiveness potential as a filamentous fungal chassis to produce proteins from other species (e.g., human albumin and interferon α-2b, SARS-CoV-2 N antigen) in virtue of the excellent expression and secretion system acquired during the studies about (hemi)cellulase production. However, all the achievements in high yield of (hemi)cellulases are impossible to finish without high-efficiency genetic strategies to analyze the proper functions of those genes involved in (hemi)cellulase gene expression or secretion. Here, we in detail summarize the current strategies employed to investigate gene functions in T. reesei. These strategies are supposed to be beneficial for extending the potential of T. reesei in prospective strain engineering.


Subject(s)
COVID-19 , Cellulase , Humans , Prospective Studies , SARS-CoV-2
8.
Nat Commun ; 14(1): 2671, 2023 05 11.
Article in English | MEDLINE | ID: covidwho-2315617

ABSTRACT

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.


Subject(s)
COVID-19 , Animals , Cricetinae , Phylogeny , SARS-CoV-2/genetics , Amino Acid Substitution , Biological Assay , Antibodies, Neutralizing , Antibodies, Viral
9.
Sci China Life Sci ; 2023 Apr 14.
Article in English | MEDLINE | ID: covidwho-2297189

ABSTRACT

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

10.
Infect Dis Model ; 8(2): 356-373, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2306362

ABSTRACT

In this paper, a stochastic COVID-19 model with large-scale nucleic acid detection and isolation measures is proposed. Firstly, the existence and uniqueness of the global positive solution is obtained. Secondly, threshold criteria for the stochastic extinction and persistence in the mean with probability one are established. Moreover, a sufficient condition for the existence of unique ergodic stationary distribution for any positive solution is also established. Finally, numerical simulations are carried out in combination with real COVID-19 data from Urumqi, China and the theoretical results are verified.

11.
Chemosphere ; 331: 138753, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2295299

ABSTRACT

Since the coronavirus disease 2019 (COVID-19) pandemic epidemic, the excessive usage of chlorinated disinfectants raised the substantial risks of disinfection by-products (DBPs) exposure. While several technologies may remove the typical carcinogenic DBPs, trichloroacetic acid (TCAA), their application for continuous treatment is limited due to their complexity and expensive or hazardous inputs. In this study, degradation and dechlorination of TCAA induced by an in situ 222 nm KrCl* excimer radiation as well as role of oxygen in the reaction pathway were investigated. Quantum chemical calculation methods were used to help predict the reaction mechanism. Experimental results showed that UV irradiance increased with increasing input power and decreased when the input power exceeded 60 W. Decomposition and dechlorination were simultaneously achieved, where around 78% of TCAA (0.62 mM) can be eliminated and 78% dechlorination within 200 min. Dissolved oxygen showed little effect on the TCAA degradation but greatly boosted the dechlorination as it can additionally generate hydroxyl radical (•OH) in the reaction process. Computational results showed that under 222 nm irradiation, TCAA was excited from S0 to S1 state and then decayed by internal crossing process to T1 state, and a reaction without potential energy barrier followed, resulting in the breaking of C-Cl bond and finally returning to S0 state. Subsequent C-Cl bond cleavage occurred by a barrierless •OH insertion and HCl elimination (27.9 kcal/mol). Finally, the •OH attacked (14.6 kcal/mol) the intermediate byproducts, leading to complete dechlorination and decomposition. The KrCl* excimer radiation has obvious advantages in terms of energy efficiency compared to other competitive methods. These results provide insight into the mechanisms of TCAA dechlorination and decomposition under KrCl* excimer radiation, as well as important information for guiding research toward direct and indirect photolysis of halogenated DBPs.


Subject(s)
COVID-19 , Disinfectants , Humans , Trichloroacetic Acid , Disinfection , Halogenation
12.
Front Psychol ; 14: 1120662, 2023.
Article in English | MEDLINE | ID: covidwho-2294457

ABSTRACT

The COVID-19 pandemic has significantly changed the teaching model, promoting educational institutions to initiate more explorations in online teaching. This study examines the factors influencing teachers' online teaching performance and satisfaction in universities during the COVID-19. We applied a model of technology acceptance (TAM), expectation confirmation (ECM), and computer self-efficacy (CSE) to develop a questionnaire. The survey was used to collect data from 347 teachers from 6 universities in eastern China to identify factors affecting teachers' performance and satisfaction during the COVID-19. The results indicated that teachers' performance of online teaching is significantly affected by satisfaction, perceived usefulness, and perceived ease of use of online teaching. Meanwhile, confirmation of online teaching expectations and computer self-efficacy significantly impacted teachers' satisfaction with online teaching. This work is an original empirical study guided by multiple theories. It contributes to the online education literature and provides advice regarding how teachers' online teaching satisfaction and performance can be developed in a situation like the one that occurred with COVID-19. This work also broadens the application of TAM and provides an alternative theoretical framework for future research on teachers' online teaching performance.

13.
Front Environ Sci Eng ; 17(9): 114, 2023.
Article in English | MEDLINE | ID: covidwho-2305476

ABSTRACT

Organic aerosol (OA) is a major component of atmospheric particulate matter (PM) with complex composition and formation processes influenced by various factors. Emission reduction can alter both precursors and oxidants which further affects secondary OA formation. Here we provide an observational analysis of secondary OA (SOA) variation properties in Yangtze River Delta (YRD) of eastern China in response to large scale of emission reduction during Chinese New Year (CNY) holidays from 2015 to 2020, and the COVID-19 pandemic period from January to March, 2020. We found a 17% increase of SOA proportion during the COVID lockdown. The relative enrichment of SOA is also found during multi-year CNY holidays with dramatic reduction of anthropogenic emissions. Two types of oxygenated OA (OOA) influenced by mixed emissions and SOA formation were found to be the dominant components during the lockdown in YRD region. Our results highlight that these emission-reduction-induced changes in organic aerosol need to be considered in the future to optimize air pollution control measures. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11783-023-1714-0 and is accessible for authorized users.

14.
Frontiers in public health ; 11, 2023.
Article in English | EuropePMC | ID: covidwho-2288565

ABSTRACT

In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.

15.
Journal of Guangxi Normal University Natural Science Edition ; 39(6):24-32, 2021.
Article in Chinese, English | GIM | ID: covidwho-2284103

ABSTRACT

Under the COVID-19 epidemic situation, the volume of road freight has declined significantly, and road operations have changed complexly. It is urgent to scientifically predict the volume of road freight. Through gray correlation analysis, the main factors affecting road freight volume during the epidemic period are determined, and a road freight volume forecast method based on the gray combination(GC)-revised BP neural network(rBPNN) model is constructed. The BP neural network is trained and tested based on the statistical data of China's road freight volume from July 2017 to May 2020 as the original data, and the "correction coefficient" HM is introduced to modify the predicting result. Based on the data of the past five months during the epidemic, the gray combined model is used to predict the value of the main factors affecting the road freight volume in the next month, and the BP neural network is used to predict China's road freight volume in June 2020. Compared the GC-rBPNN model with other prediction methods, the PE and MAPE of the GC-rBPNN model are 0.21% and 3.21%, respectively. The results show that the prediction accuracy of the GC-rBPNN model is higher, and the method has certain feasibility and effectiveness.

16.
Nano Res ; : 1-9, 2022 Oct 22.
Article in English | MEDLINE | ID: covidwho-2288129

ABSTRACT

Plasmonic enhanced fluorescence (PEF) technology is a powerful strategy to improve the sensitivity of immunofluorescence microarrays (IFMA), however, current approaches to constructing PEF platforms are either expensive/time-consuming or reliant on specialized instruments. Here, we develop a completely alternative approach relying on a two-step protocol that includes the self-assembly of gold nanoparticles (GNPs) at the water-oil interface and subsequent annealing-assisted regulation of gold nanogap. Our optimized thermal-annealing GNPs (TA-GNP) platform generates adequate hot spots, and thus produces high-density electromagnetic coupling, eventually enabling 240-fold fluorescence enhancement of probed dyes in the near-infrared region. For clinical detection of human samples, TA-GNP provides super-high sensitivity and low detection limits for both hepatitis B surface antigen and SARS-CoV-2 binding antibody, coupled with a much-improved detection dynamic range up to six orders of magnitude. With fast detection, high sensitivity, and low detection limit, TA-GNP could not only substantially improve the outcomes of IFMA-based precision medicine but also find applications in fields of proteomic research and clinical pathology. Electronic Supplementary Material: Supplementary material (UV-Vis absorption and transmission spectra of GNPs, SEM, microscopy and digital images of PEF platforms, and fluorescence images of IFMA on PEF platforms) is available in the online version of this article at 10.1007/s12274-022-5035-6.

17.
Front Public Health ; 11: 1137489, 2023.
Article in English | MEDLINE | ID: covidwho-2288566

ABSTRACT

In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.


Subject(s)
COVID-19 , Humans , Cities , COVID-19/epidemiology , Environment Design , Built Environment , Linear Models
18.
Chemistry ; 29(35): e202300476, 2023 Jun 22.
Article in English | MEDLINE | ID: covidwho-2286075

ABSTRACT

SARS-CoV-2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (Mpro ) is essential in the replication of SARS-CoV-2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics-constrained α, γ-AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the Mpro of SARS-CoV-2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET-based Mpro enzymatic assay not only for the Mpro of SARS-CoV-2 but also for SARS-CoV and MERS-CoV, along with HCoVs like HCoV-OC43, HCoV-229E, HCoV-NL63 and HKU1. The X-ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS-CoV-2. Overall, the results suggest that α, γ-AA peptide could be a promising molecular scaffold in designing novel Mpro inhibitors of SARS-CoV-2 and other coronaviruses.


Subject(s)
COVID-19 , Coronavirus OC43, Human , Humans , SARS-CoV-2 , Peptides/pharmacology , Antiviral Agents/pharmacology , Protease Inhibitors/chemistry
19.
Ageing Res Rev ; 87: 101921, 2023 06.
Article in English | MEDLINE | ID: covidwho-2252164

ABSTRACT

The complex structure of the blood-brain barrier (BBB) hinders its modeling and the treatment of brain diseases. The microfluidic technology promotes the development of BBB-on-a-chip platforms, which can be used to reproduce the complex brain microenvironment and physiological reactions. Compared with traditional transwell technology, microfluidic BBB-on-a-chip shows great technical advantages in terms of flexible control of fluid shear stress in the chip and fabrication efficiency of the chip system, which can be enhanced by the development of lithography and three-dimensional (3D) printing. It is convenient to accurately monitor the dynamic changes of biochemical parameters of individual cells in the model by integrating an automatic super-resolution imaging sensing platform. In addition, biomaterials, especially hydrogels and conductive polymers, solve the limitations of microfluidic BBB-on-a-chip by compounding onto microfluidic chip to provide a 3D space and special performance on the microfluidic chip. The microfluidic BBB-on-a-chip promotes the development of basic research, including cell migration, mechanism exploration of neurodegenerative diseases, drug barrier permeability, SARS-CoV-2 pathology. This study summarizes the recent advances, challenges and future prospects of microfluidic BBB-on-a-chip, which can help to promote the development of personalized medicine and drug discovery.


Subject(s)
COVID-19 , Microfluidic Analytical Techniques , Humans , Blood-Brain Barrier , Microfluidics , Microfluidic Analytical Techniques/methods , SARS-CoV-2
20.
ACS Appl Mater Interfaces ; 2023 Feb 13.
Article in English | MEDLINE | ID: covidwho-2262158

ABSTRACT

Developing a rapid antibody-based detection method is of great importance for preventing and controlling the spread of coronavirus disease 2019 (COVID-19). Among the antibody-based methods for point-of-care (POC) detection, lateral flow immunoassay (LFIA) is the most widely used. However, LFIA still has the disadvantage of low sensitivity. In this work, an ReSe2 nanosheet with a thickness of 10-20 nm was prepared by liquid exfoliation and applied as the label in a photothermal LFIA due to its high photothermal conversion efficiency and high photothermal stability. An integrated detection device was introduced for rapid, on-site, and highly sensitive assay of the human antisevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein IgG antibodies. The device mainly included a rhenium diselenide (ReSe2) nanosheet-based photothermal LFIA, a portable laser, and a smartphone with a portable thermal imager, which was used to record and analyze the thermal signal of the LFIA test zone. The human anti-SARS-COV-2 S protein IgG antibodies in buffer solution can be detected in a portable box within 10 min, with a thermal signal detection limit of 0.86 ng mL-1, which was 108-fold lower than that of the colorimetric signal. The integrated device can detect values as low as 2.76 ng mL-1 of the human anti-SARS-COV-2 S protein IgG antibodies in 50% serum. The integrated device showed great potential for rapid and home self-testing diagnosis of COVID-19.

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