1.A Survey on the Perceived Experience and Acceptance of Intrapartum Ultrasound as a Novel Method for Labor Progress Assessment
Xinjuan CHEN ; Jinhui CUI ; Liping OUYANG ; Ling LI ; Jianhui FAN ; Ping LI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):535-540
ObjectiveTo investigate the perceived experience and acceptance of intrapartum ultrasound (IPUS) as a novel method for labor progress assessment among pregnant women. MethodsFrom February 2023 to December 2024, a total of 180 pregnant women admitted to the Labor Ward of Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University, who were planned for vaginal trial of labor , were accessed for labor progress using IPUS and vaginal examination (VE) after the onset of labor and prior to the initiation n of labor analgesia. A self-designed questionnaire was used to investigate the women's perceived experiences with both examination methods and their acceptance of IPUS. The pain intensity associated with the examinations was evaluated using the visual analogue pain scale (VAS). Differences in the women's experiences and pain intensity between the two labor progress assessment methods were compared. ResultsThe acceptance rate of IPUS was 96.67% (174/180), with the remaining 6 cases undecided. Over 60% of the pregnant women reported IPUS assessment as comfortable and none of them felt discomfort, whereas 32.8% felt uncomfortable with VE (χ2=196.02, P<0.001). Nearly two-thirds of the pregnant women believed that VE would cause psychological distress, while none reported such effect with IPUS (χ2=261.52, P<0.001). Approximately 77.78% (140/180) of the pregnant women believed that IPUS could reduce their fear of vaginal delivery and enhance their confidence if it replaced VE. The VAS score for IPUS [0 (0, 2)] was significantly lower than that for VE [4 (4, 6)] (Z=-14.62, P<0.001). Further stratified analysis showed that over 90% (164/180) of the pregnant women found IPUS painless, with no moderate or severe pain reported, compared to 43.33% (78/180) experienced moderate or severe pain with VE (P<0.001). ConclusionAs a novel approach for labor progress assessment, IPUS not only alleviates the pain and discomfort associated with traditional VE and reduces the fear of childbirth but also enhances women's confidence in delivery, thereby achieving a high level of acceptance among parturient women in China.
2.Clinical trial of omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer
San-Li FAN ; Hai-Yan HU ; Cui JIN ; Jing-Jie BAI ; Fang DONG ; Jin-Fang SUN ; Yan QIN ; Xiao-Ling MENG ; Hui-Qin XUE
The Chinese Journal of Clinical Pharmacology 2024;40(7):973-976
Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74%(45 cases/48 cases)and 85.42%(41 cases/48 cases),with significant difference(P<0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33%and 12.50%,with no statistical significance(P>0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.
3.The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure
Tao HONG ; Wei SUN ; Yuan DENG ; Da Jian LYU ; Hong Cui JIN ; Long Ying BAI ; Jun NA ; Rui ZHANG ; Yuan GAO ; Wei Guo PAN ; Sen Zuo YANG ; Jun Ling YAN
Biomedical and Environmental Sciences 2024;37(1):31-41
Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres (100 nm, 3 μm, and 10 μm) were given once at a dose of 200 mg/(kg·body weight). The fluorescence intensity (FI) in observed organs was measured using the IVIS Spectrum at 0.5, 1, 2, and 4 h after administration. Histopathology was performed to corroborate these findings.Results In the 100 nm group, the FI of the stomach and small intestine were highest at 0.5 h, and the FI of the large intestine, excrement, lung, kidney, liver, and skeletal muscles were highest at 4 h compared with the control group (P < 0.05). In the 3 μm group, the FI only increased in the lung at 2 h (P < 0.05). In the 10 μm group, the FI increased in the large intestine and excrement at 2 h, and in the kidney at 4 h (P < 0.05). The presence of nano-/microplastics in tissues was further verified by histopathology. The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however, only small amounts of MPs could penetrate the organs.
4.A diagnostic prediction model for hypertension in Han and Yugur population from the China National Health Survey (CNHS).
Chengdong YU ; Xiaolan REN ; Ze CUI ; Li PAN ; Hongjun ZHAO ; Jixin SUN ; Ye WANG ; Lijun CHANG ; Yajing CAO ; Huijing HE ; Jin'en XI ; Ling ZHANG ; Guangliang SHAN
Chinese Medical Journal 2023;136(9):1057-1066
BACKGROUND:
The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies.
METHODS:
The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model.
RESULTS:
The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population.
CONCLUSION
This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult
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Humans
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Asian People
;
China/epidemiology*
;
Cross-Sectional Studies
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Health Surveys
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Hypertension/epidemiology*
;
Nomograms
;
Ethnicity
5.Echocardiographic diagnosis of sinus of Valsalva aneurysm
Rui FAN ; Jie LI ; Cui-ling LI ; Hong LIN ; Feng-juan YAO
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):169-174
ObjectiveTo summarize the echocardiographic features of sinus of Valsalva aneurysm (SVA), analyze the causes of missed diagnosis, thus explore the diagnostic skills and improve the diagnostic accuracy for SVA. MethodsThe echocardiographic features and clinical data of 52 SVA patients who underwent surgery in the First Affiliated Hospital of Sun Yat-sen University from January 2014 to March 2022 were retrospectively reviewed. The patients were divided into 5 types according to modified Sakakibara classification system. ResultsThere were 32 male and 20 female patients with their age of 18~66 (36.1±11.6) years. Of the 52 aneurysms, 44 originated from the right coronary sinus (RCS), 8 from noncoronary sinus (NCS) and none from left coronary sinus (LCS). Among the 35 SVAs protruding into the right ventricle, including type I, type Ⅱ and type Ⅲv, 32 (91.4%) were associated with ventricular septal defect (VSD). There were 2 (17.6%) associated with VSD among the 17 SVAs protruding into the right atrium or other sites of the heart, including type Ⅲa, type Ⅳ and type Ⅴ. SVA was frequently associated with aortic valve disease, 27 cases (51.9%) of which needed surgical valve replacement or valvoplasty. SVA was missed in 4 patients and VSD in 8, with the misdiagnosis rates of 7.7% and 23.5%, respectively. The most commonly missed VSD diagnosis was subarterial VSD with type I SVA. Of the 19 SVAs associated with infective endocarditis (IE), 2 were missed, with the misdiagnosis rate of 10.5%. ConclusionThe ultrasound images of SVA are diverse and complex. SVA protruding into the right atrium is rarely associated with VSD, while SVA protruding into the right ventricle is frequently associated with VSD. SVA is also prone to be associated with aortic valve disease and IE, which makes the diagnosis more challenging. Therefore, during ultrasound examination, we must vigilantly and flexibly make use of the multiple scan slices so as to decrease the rate of missed diagnosis and improve the diagnostic accuracy for SVA.
6.Toxicity evaluation of zinc oxide nanoparticles in vitro and in vivo on cornea
Xiao-Lu HOU ; Dong-Mei CUI ; Ling-Zhi NIU ; Xiao-Tong SUN ; Tao YU ; Yu-Hang ZHAO ; Ai-Ping SONG ; Wei LI
International Eye Science 2023;23(7):1080-1086
AIM:To observe the toxic effects of zinc oxide nanoparticles(ZnO NPs)on cornea by constructing intoxicated model in vivo and in vitro.METHODS:Human corneal epithelial cells(HCEpiC)were cultured in vitro and exposed to different concentrations(0.5, 5, 12.5, 25, 50, 100, 250 μg/mL)of ZnO NPs for 24h. The cell culture medium without nano-solution was used as the blank control group. The viability of the cells was assessed by MTT assay. Three different concentrations(25, 50 and 100 μg/mL)of ZnONPs dispersions were exposed to the conjunctival sac of anesthetized mice three times a day for 7d consecutively. The phosphate buffered saline(PBS)eye group was the PBS control group. Corneal morphology was observed on 1, 3, 5 and 7d, and the eyes were removed on 8d for various laboratory examinations, including corneal pathological changes and expression levels of inflammatory factors(TNF-α, IL-6).RESULTS:After treatment of HCEpiC cells with different concentrations of ZnO NPs for 24h, the MTT results showed that Zno NPs cause damage to cells at 0.5 μg/mL, and the cell survival rate was about 80%(P<0.05). Half of the cells were killed at a dose of 5 μg/mL, the damaging effect on cells in the concentration range of 5~250 μg/mL was concentration-dependent(P<0.0001). After 7d of conjunctival capsule spotting in mice, dot-like staining of fluorescein was seen in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups. Localized circular fluorescein stained areas were seen in the corneas of the 100 μg/mL ZnO NPs group. HE staining showed that the corneal epithelial layer, stromal layer thickness and stromal layer immune cell number did not change significantly in the 25 μg/mL and 50 μg/mL ZnO NPs groups(all P>0.05), while the corneal epithelial layer thinned, the corneal stromal layer thickened and the stromal layer immune cells increased significantly in the 100 μg/mL ZnO NPs group(all P<0.05). Immunohistochemical staining showed that the number of corneal stromal immune cells producing TNF-α and IL-6 and the mean integral optical density(IOD)values of TNF-α and IL-6 were significantly higher in the 100 μg/mL ZnO NPs group than in the PBS control group(P<0.05), and the degree of inflammation response was concentration-dependent. Compared with the PBS control group, no significant increase in immune cell count and IOD values in the 25 μg/mL ZnO NPs and 50 μg/mL ZnO NPs groups(P>0.05).CONCLUSION:The toxic damaging effect of ZnO NPs on the cornea was confirmed from both in vitro and in vivo, which provided a theoretical basis for the ocular safety evaluation of ZnO NPs.
7.Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China.
Xin Cheng CAO ; Si Yuan JIANG ; Shu Juan LI ; Jun Yan HAN ; Qi ZHOU ; Meng Meng LI ; Rui Miao BAI ; Shi Wen XIA ; Zu Ming YANG ; Jian Fang GE ; Bao Quan ZHANG ; Chuan Zhong YANG ; Jing YUAN ; Dan Dan PAN ; Jing Yun SHI ; Xue Feng HU ; Zhen Lang LIN ; Yang WANG ; Li Chun ZENG ; Yan Ping ZHU ; Qiu Fang WEI ; Yan GUO ; Ling CHEN ; Cui Qing LIU ; Shan Yu JIANG ; Xiao Ying LI ; Hui Qing SUN ; Yu Jie QI ; Ming Yan HEI ; Yun CAO
Chinese Journal of Pediatrics 2023;61(1):29-35
Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant
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Infant, Newborn
;
Humans
;
Birth Weight
;
Intensive Care Units, Neonatal
;
Retrospective Studies
;
Tertiary Care Centers
;
Infant, Extremely Low Birth Weight
;
Gestational Age
;
Infant, Extremely Premature
;
Sepsis/epidemiology*
;
Retinopathy of Prematurity/epidemiology*
;
Bronchopulmonary Dysplasia/epidemiology*
8.Clinical features and prognosis of core binding factor acute myeloid leukemia children in South China: a multicenter study.
Bi Yun GUO ; Yue WANG ; Jian LI ; Chun Fu LI ; Xiao Qin FENG ; Min Cui ZHENG ; Si Xi LIU ; Li Hua YANG ; Hua JIANG ; Hong Gui XU ; Xiang Ling HE ; Hong WEN
Chinese Journal of Pediatrics 2023;61(10):881-888
Objective: To analyze the clinical features, efficacy and prognosis factors of core binding factor (CBF) acute myeloid leukemia (AML) children in South China. Methods: This was a retrospective cohort study. Clinical data of 584 AML patients from 9 hospitals between January 2015 to December 2020 was collected. According to fusion gene results, all patients were divided into two groups: CBF-AML group (189 cases) and non-CBF-AML group (395 cases). CBF-AML group were divided into AML1-ETO subgroup (154 cases) and CBFβ-MYH11 subgroup (35 cases). Patients in CBF-AML group chosen different induction scheme were divided into group A (fludarabine, cytarabine, granulocyte colony stimulating factor and idarubicin (FLAG-IDA) scheme, 134 cases) and group B (daunorubicin, cytarabine and etoposide (DAE) scheme, 55 cases). Age, gender, response rate, recurrence rate, mortality, molecular genetic characteristics and other clinical data were compared between groups. Kaplan-Meier method was used for survival analysis and survival curve was drawn. Cox regression model was used to analyze prognostic factors. Results: A total of 584 AML children were diagnosed, including 346 males and 238 females. And a total of 189 children with CBF-AML were included, including 117 males and 72 females. The age of diagnosis was 7.3 (4.5,10.0)years, and the white blood cell count at initial diagnosis was 21.4 (9.7, 47.7)×109/L.The complete remission rate of the first course (CR1) of induction therapy, relapse rate, and mortality of children with CBF-AML were significantly different from those in the non-CBF-AML group (91.0% (172/189) vs. 78.0% (308/395); 10.1% (19/189) vs. 18.7% (74/395); 13.2% (25/189) vs. 25.6% (101/395), all P<0.05). In children with CBF-AML, the CBFβ-MYH11 subgroup had higher initial white blood cells and lower proportion of extramedullary invasion than the AML1-ETO subgroup, with statistical significance (65.7% (23/35) vs. 14.9% (23/154), 2.9% (1/35) vs. 16.9% (26/154), both P<0.05). AML1-ETO subgroup had more additional chromosome abnormalities (75/154), especially sex chromosome loss (53/154). Compared with group B, group A had more additional chromosome abnormalities and a higher proportion of tumor reduction regimen, with statistical significance (50.0% (67/134) vs. 29.1% (16/55), 34.3% (46/134) vs. 18.2% (10/55), both P<0.05). Significant differences were found in 5-years event free survival (EFS) rate and 5-year overall survival (OS) rate between CBF-AML group and non-CBF-AML group ((77.0±6.4)%vs. (61.9±6.7)%,(83.7±9.0)%vs. (67.3±7.2)%, both P<0.05).EFS and OS rates of AML1-ETO subgroup and CBFβ-MYH11 subgroup in children with CBF-AML were not significantly different (both P>0.05). Multivariate analysis showed in the AML1-ETO subgroup, CR1 rate and high white blood cell count (≥50×109/L) were independent risk factors for EFS (HR=0.24, 95%CI 0.07-0.85,HR=1.01, 95%CI 1.00-1.02, both P<0.05) and OS (HR=0.24, 95%CI 0.06-0.87; HR=1.01, 95%CI 1.00-1.02; both P<0.05). Conclusions: In CBF-AML, AML1-ETO is more common which has a higher extramedullary involvement and additional chromosome abnormalities, especially sex chromosome loss. The prognosis of AML1-ETO was similar to that of CBFβ-MYH11. The selection of induction regimen group FLAG-IDA for high white blood cell count and additional chromosome abnormality can improve the prognosis.
Male
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Female
;
Humans
;
Child
;
Retrospective Studies
;
RUNX1 Translocation Partner 1 Protein/genetics*
;
Core Binding Factor Alpha 2 Subunit/therapeutic use*
;
Prognosis
;
Leukemia, Myeloid, Acute/genetics*
;
Cytarabine/therapeutic use*
;
Oncogene Proteins, Fusion/genetics*
;
Chromosome Aberrations
9.Interpretation of presynaptic dopaminergic PET imaging results
Ping WU ; Jianjun WU ; Xun SUN ; Jingjie GE ; Fangyang JIAO ; Chengfeng JIANG ; Lirong JIN ; Xinlu WANG ; Zhenguang WANG ; Yafu YIN ; Ruixue CUI ; Rong TIAN ; Shuo HU ; Rongbing JIN ; Jianjun LIU ; Xiangsong ZHANG ; Ling CHEN ; Jie LU ; Xingmin HAN ; Yihui GUAN ; Xiaoli LAN ; Chuantao ZUO ; Jian WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(4):236-241
Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.
10.Targeting papain-like protease for broad-spectrum coronavirus inhibition.
Shuofeng YUAN ; Xiaopan GAO ; Kaiming TANG ; Jian-Piao CAI ; Menglong HU ; Peng LUO ; Lei WEN ; Zi-Wei YE ; Cuiting LUO ; Jessica Oi-Ling TSANG ; Chris Chun-Yiu CHAN ; Yaoqiang HUANG ; Jianli CAO ; Ronghui LIANG ; Zhenzhi QIN ; Bo QIN ; Feifei YIN ; Hin CHU ; Dong-Yan JIN ; Ren SUN ; Jasper Fuk-Woo CHAN ; Sheng CUI ; Kwok-Yung YUEN
Protein & Cell 2022;13(12):940-953
The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals
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Coronavirus Papain-Like Proteases/antagonists & inhibitors*
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Cricetinae
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Humans
;
Mice
;
Pandemics
;
SARS-CoV-2/enzymology*
;
COVID-19 Drug Treatment

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