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HGNC Genes

SARS-CoV-2 proteins

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    Isothermal Recombinase Polymerase Amplification-lateral Flow Detection of SARS-CoV-2, the Etiological Agent of COVID-19 MESHD

    Authors: Thomas R Shelite; Ashanti C Uscanga-Palomeque; Alejandro Castellanos; Peter C Melby; Bruno L Travi

    doi:10.21203/rs.3.rs-78408/v2 Date: 2020-09-15 Source: ResearchSquare

    The rapid detection of novel pathogens necessitates the development of easy-to-use diagnostic tests that can be readily adapted and utilized in both clinical laboratories and field settings. In December of 2019, novel coronavirus, SARS-CoV-2 (2019-nCoV), was isolated from a cluster of pneumonia MESHD patients in the Chinese city of Wuhan. The virus rapidly spread throughout the world and the first fatal cases of COVID-19 MESHD in the United States occurred in late February. The lack of testing and delay in diagnosis has facilitated the spread of this novel virus. Development of point-of-care diagnostic assays that can be performed in rural or decentralized health care centers to expand testing capacity is needed. We developed a qualitative test based on recombinase-polymerase-amplification coupled with lateral flow reading (RPA-LF) for rapid detection of SARS-CoV-2. The RPA-LF detected SARS-CoV-2 with a limit of detection of 35.4 viral nucleocapsid (N PROTEIN) gene copies/µL. Additionally, the RPA-LF was able to detect 0.25-2.5 copies/µL of SARS-CoV-2 N gene PROTEIN containing plasmid. We evaluated 37 clinical samples using CDC’s N3, N1 and N2 RT-real-time PCR assays for SARS-CoV-2 as reference test. We found a 100% concordance between RPA-LF and RT-qPCR reference test as determined by 18/18 positive and 19/19 negative samples. All positive samples had Ct values between 19-37 by RT-qPCR. The RPA-LF primers and probe did not cross react with other relevant betacoronaviruses such as SARS and MERS. This is the first isothermal amplification test paired with lateral flow developed for qualitative detection of COVID-19 MESHD allowing rapid viral detection and with prospective applicability in resource limited and decentralized laboratories.

    Neutralizing antibody-dependent and -independent immune responses against SARS-CoV-2 in cynomolgus macaques

    Authors: Hirohito Ishigaki; Misako Nakayama; Yoshinori Kitagawa; Cong Thanh Nguyen; Kaori Hayashi; Masanori Shiohara; Bin Gotoh; Yasushi Itoh; Osemeke Osokogu; Magdalena Skrybant; Jonathan J Deeks; Katie L Flanagan; Denise Doolan; Joseph Torresi; Weisan Chen; Linda Wakim; Allen Cheng; Jan Petersen; Jamie Rossjohn; Adam K Wheatley; Stephen Kent; Louise Rowntree; Katherine Kedzierska; Mengge Lyu; Guixiang Xiao; Xia Xu; Weigang Ge; Jiale He; Jun Fan; Junhua Wu; Meng Luo; Xiaona Chang; Huaxiong Pan; Xue Cai; Junjie Zhou; Jing Yu; Huanhuan Gao; Mingxing Xie; Sihua Wang; Guan Ruan; Hao Chen; Hua Su; Heng Mei; Danju Luo; Dashi Zhao; Fei Xu; Yan Li; Yi Zhu; Jiahong Xia; Yu Hu; Tiannan Guo

    doi:10.1101/2020.08.18.256446 Date: 2020-08-19 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectious disease MESHD ( COVID-19 MESHD) has been threatening the world because of severe symptoms and relatively high mortality. To develop vaccines and antiviral drugs for COVID-19 MESHD, an animal model of SARS-CoV-2 infection MESHD is required to evaluate the efficacy of prophylactics and therapeutics in vivo. Therefore, we examined the pathogenicity of SARS-CoV-2 in cynomolgus macaques until 28 days after virus inoculation in the present study. Cynomolgus macaques showed body temperature rises after infection and X-ray radiographic viral pneumonia MESHD was observed in one of three macaques. However, none of the macaques showed life-threatening clinical signs of disease corresponding that approximately 80% of human patients did not show a critical disease in COVID-19 MESHD. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes that produced interferon (IFN)-{gamma} and interleukin (IL)-2 specifically for SARS-CoV-2 N MESHD N protein PROTEIN were detected on day 14 in the macaque that showed viral pneumonia MESHD. On the other hand, in the other macaques, in which a neutralizing antibody was not detected, T-lymphocytes that produced IFN-{gamma HGNC} specifically for SARS-CoV-2 N MESHD N protein PROTEIN increased on day 7 to day 14 prior to an increase in the number of T-lymphocytes that produced IL-2 HGNC. These results suggest that not only a neutralizing antibody but also cellular immunity augmented by IFN-{gamma HGNC} has a role in the elimination of SARS-CoV-2. Thus, because of the mild clinical signs of disease and low/no antibody responses against SARS-CoV-2 in two thirds of the macaques, cynomolgus macaques are appropriate to extrapolate human responses in vaccine and drug development. Author SummarySevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectious disease ( COVID-19 MESHD) has been threatening the world. To develop vaccines and antiviral drugs for COVID-19 MESHD, an animal model of SARS-CoV-2 infection MESHD is required to evaluate their efficacy in vivo. Therefore, we examined the pathogenicity of SARS-CoV-2 in a non-human primate model until 28 days after virus inoculation. Cynomolgus macaques showed a fever after infection and X-ray radiographic viral pneumonia was observed in one of three macaques. However, none of the macaques showed life-threatening symptoms. A neutralizing antibody against SARS-CoV-2 and T-lymphocytes that produced interferon (IFN)-{gamma} and interleukin (IL)-2 specifically for SARS-CoV-2 protein were detected on day 14 in the macaque that showed viral pneumonia. In the other macaques, in which a neutralizing antibody was not detected, T-lymphocytes that produced IFN-{gamma HGNC} specifically for SARS-CoV-2 N protein PROTEIN increased on day 7 to day 14. These results suggest that not only a neutralizing antibody but also cellular immunity augmented by IFN-{gamma HGNC} has a role in the elimination of SARS-CoV-2. Thus, because of the mild symptoms and low/no antibody responses against SARS-CoV-2 in two thirds of the macaques, cynomolgus macaques are appropriate to extrapolate human responses in vaccine and drug development.

    Optimized Laboratory Detection Strategy for COVID-19 MESHD Patients Reduces the Rate of Missed Diagnosis

    Authors: Wenjiao Chang; Yuru Shi; Yingjie Qi; Jiaxing Liu; Ting Liu; Zhaowu Chen; Dongfeng Liu; Ming Yin; Jing Xu; Yun Yang; Jing Ge; Shu Zhu; Yong Gao; Xiaoling Ma

    doi:10.21203/rs.3.rs-42485/v1 Date: 2020-07-13 Source: ResearchSquare

    Background: Novel coronavirus pneumonia MESHD ( NCP PROTEIN) is an emerging, highly contagious community acquired pneumonia MESHD (CAP) caused by severe acute SARS-CoV-2. Nucleic acid test currently played a crucial role in diagnosis of suspected COVID-19 MESHD patients. However, a high false-negative rate of this “gold standard” test has been reported and posed a major setback in blocking the spread of the virus. We here aim to describe an optimized laboratory detection strategy to reduce the false negative rate. Methods: Suspected NCP PROTEIN patients were asked to collect both coughed up specimen and pharyngeal swab. Samples from the same patient were mixed and tested at a single pool. SARS-CoV-2 was then detected by real-time RT-PCR using two different detection kits. Only if both results were negative was the test reported as negative. The patients will be excluded after two consecutive negative tests at 24 hour intervals. We also used multiplex PCR to detect 13 common respiratory tract pathogens ( RTP HGNC). Results: Using this strategy, we confirmed 85 SARS-CoV-2 infections MESHD from 181 suspected patients, and 94.12% of patients were positive in the first test. The 96 excluded patients were followed up, and no additional NCP PROTEIN was found. We also found that 31.25% patients in 96 non- NCP PROTEIN patients were infected MESHD with at least one RTP HGNC that may cause CAP. Conclusion: Our studies suggest that dual reagents screening with pooled coughed up specimen and pharyngeal swab samples reduced the false negative rate of nucleic acid testing. During the epidemic of NCP PROTEIN in Anhui province, there was a certain proportion of infection and co-infection MESHD of other common pathogens of CAP. In comparison with SARS-CoV-2 detection alone, combining multiple pathogen detection reduces the rate of miss diagnosis.

    Alarming Symptoms Leading To Severe COVID-19 MESHD Pneumonia: A Meta-Analysis

    Authors: Weiping Ji; Jing Zhang; Gautam Bishnu; Xudong Du; Xinxin Chen; Hui Xu; Xiaoling Guo; Zhenzhai Cai; Jun Zhang; Xian Shen

    doi:10.21203/rs.3.rs-35449/v1 Date: 2020-06-14 Source: ResearchSquare

    Background: To identify alarming symptoms that could potentially lead to severe form of COVID-19 MESHD pneumonia MESHD (i.e. novel coronavirus pneumonia MESHD: NCP PROTEIN), a disease that is now having pandemic spread.Methods: Articles from PubMed, Embase, Cochrane database and Google up to 24 February 2020 were systematically reviewed. 18 publications that had documented cases of COVID-19 MESHD pneumonia MESHD were identified. The relevant data were extracted, systematically reviewed and further evaluated using meta-analysis. We define severe COVID-19 MESHD pneumonia MESHD as the disease status that requires admission to the intensive care unit (ICU) and respiratory/circulatory support, which is in align with the guideline from the World Health Organization (WHO).Results: 14 studies including 1,424 patients were considered eligible and analyzed. Symptoms such as fever MESHD (89.2%), cough (67.2%), fatigue MESHD (43.6%) were quite common; but dizziness MESHD, hemoptysis, abdominal pain MESHD and conjunctival congestion/ conjunctivitis MESHD were relatively rare. The incidence of dyspnea MESHD was significantly higher in patients with severe than non-severe COVID-19 MESHD pneumonia MESHD (42.7% vs.16.3%, p<0.0001). Similarly, fever MESHD and diarrhea MESHD were also drastically more common in patients with severe form (p=0.0374 and 0.0267). Further meta-analysis using three high-quality China-based studies confirmed such findings and showed that dyspnea MESHD, fever MESHD and diarrhea MESHD were 3.53 (OR: 3.53, 95%CI: 1.95-6.38), 1.70 (OR: 1.70, 95%CI: 1.01-2.87), and 1.80 (OR: 1.80, 95%CI: 1.06-3.03) folds higher respectively in patients with severe COVID-19 MESHD pneumonia MESHD.Conclusion: Dyspnea, fever MESHD and diarrhea MESHD are significantly more prevalent in patients with severe COVID-19 MESHD pneumonia MESHD, suggesting they are alarming symptoms that warrant close attention and timely management.

    Benchmarking Deep Learning Models and Automated Model Design for COVID-19 MESHD Detection with Chest CT Scans

    Authors: Xin He; Shihao Wang; Shaohuai Shi; Xiaowen Chu; Jiangping Tang; Xin Liu; Chenggang Yan; Jiyong Zhang; Guiguang Ding

    doi:10.1101/2020.06.08.20125963 Date: 2020-06-09 Source: medRxiv

    COVID-19 pandemic MESHD COVID-19 pandemic MESHD has spread all over the world for months. As its transmissibility and high pathogenicity seriously threaten people's lives, the accurate and fast detection of the COVID-19 MESHD infection is crucial. Although many recent studies have shown that deep learning based solutions can help detect COVID-19 MESHD based on chest CT scans, there lacks a consistent and systematic comparison and evaluation on these techniques. In this paper, we first build a clean and segmented CT dataset called Clean-CC-CCII by fixing the errors and removing some noises in a large CT scan dataset CC-CCII with three classes: novel coronavirus pneumonia MESHD ( NCP PROTEIN), common pneumonia MESHD (CP), and normal controls (Normal). After cleaning, our dataset consists of a total of 340,190 slices of 3,993 scans from 2,698 patients. Then we benchmark and compare the performance of a series of state-of-the-art (SOTA) 3D and 2D convolutional neural networks (CNNs). The results show that 3D CNNs outperform 2D CNNs in general. With extensive effort of hyperparameter tuning, we find that the 3D CNN model DenseNet3D121 achieves the highest accuracy of 88.63% (F1-score is 88.14% and AUC is 0.940), and another 3D CNN model ResNet3D34 achieves the best AUC of 0.959 (accuracy is 87.83% and F1-score is 86.04%). We further demonstrate that the mixup data augmentation technique can largely improve the model performance. At last, we design an automated deep learning methodology to generate a lightweight deep learning MESHD model MNas3DNet41 that achieves an accuracy of 87.14%, F1-score of 87.25%, and AUC of 0.957, which are on par with the best models made by AI experts. The automated deep learning design is a promising methodology that can help health-care professionals develop effective deep learning models using their private data sets. Our Clean-CC-CCII dataset and source code are available at: https://github.com/arthursdays/HKBU\_HPML\_ COVID-19 MESHD.

    High-Content Screening of Thai Medicinal Plants Reveals Boesenbergia rotunda Extract and its Component Panduratin A as Anti-SARS-CoV-2 Agents

    Authors: Phongthon Kanjanasirirat; Ampa Suksatu; Suwimon Manopwisedjaroen; Bamroong Munyoo; Patoomratana Tuchinda; Kedchin Jearawuttanakul; Sawinee Seemakhan; Sitthivut Charoensutthivarakul; Patompon Wongtrakoongate; Noppawan Rangkasenee; Supaporn Pitiporn; Neti Waranuch; Napason Chabang; Phisit Khemawoot; Somchai Chutipongtanate; Suradej Hongeng; Suparerk Borwornpinyo; Arunee Thitithanyanont

    doi:10.21203/rs.3.rs-32489/v1 Date: 2020-05-29 Source: ResearchSquare

    Since December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2) has caused severe pneumonia MESHD, a disease named COVID-19 MESHD, that became pandemic and created an acute threat to public health. The effective therapeutics are in urgent need. Here, we developed a high-content screening for the antiviral candidates using fluorescence-based SARS-CoV-2 nucleoprotein PROTEIN detection in Vero E6 cells coupled with plaque reduction assay. Among 122 Thai natural products, we found that Boesenbergia rotunda extract and its phytochemical compound, panduratin A, exhibited the potent anti-SARS-CoV-2 activity. Treatment with B. rotunda extract and panduratin A after viral infection drastically suppressed SARS-CoV-2 infectivity MESHD in Vero E6 cells with IC50 of 3.62 μg/mL (CC50 = 28.06 µg/mL) and 0.81 μΜ (CC50=14.71 µM), respectively. Also, the treatment of panduratin A at the pre-entry phase inhibited SARS-CoV-2 infection MESHD with IC50 of 5.30 µM (CC50=43.47 µM). Our study demonstrated, for the first time, that panduratin A exerts the inhibitory effect against SARS-CoV-2 infection MESHD at both pre-entry and post-infection phases. Since B. rotunda is a culinary herb generally grown in China and Southeast Asia, its extract and the purified panduratin A may serve as the promising candidates for therapeutic purposes with economic advantage during COVID-19 MESHD situation.

    The effects of the clinical symptoms pneumonia-confirmation strategy of the COVID-19 MESHD epidemic in Wuhan, China

    Authors: Yanjin Wang; Pei Wang; Shudao Zhang; Hao Pan

    doi:10.21203/rs.3.rs-28619/v1 Date: 2020-05-12 Source: ResearchSquare

    Motivated by the quick control in Wuhan, China, and the rapid spread in other countries of COVID-19 MESHD, we investigate the questions that what is the turning point in Wuhan by quantifying the variety of basic reproductive number after the lockdown city. The answer may help the world to control the COVID-19 MESHD epidemic. A modified SEIR model is used to study the COVID-19 MESHD epidemic in Wuhan city. Our model is calibrated by the hospitalized cases. The modeling result gives out that the means of basic reproductive numbers are 1.5517 (95% CI 1.1716-4.4283) for the period from Jan 25 to Feb 11 HGNC, 2020, and 0.4738(95% CI 0.0997-0.8370) for the period from Feb 12 to Mar 10. The transmission rate fell after Feb 12, 2020 as a result of China’s COVID-19 MESHD strategy of keeping society distance and the medical support from all China, but principally because of the clinical symptoms to be used for the novel coronavirus pneumonia MESHD ( NCP PROTEIN) confirmation in Wuhan since Feb 12, 2020. Clinical diagnosis can quicken up NCP PROTEIN-confirmation such that the COVID-19 MESHD patients can be isolated without delay. So the clinical symptoms pneumonia-confirmation is the turning point of the COVID-19 MESHD battle of Wuhan. The measure of clinical symptoms pneumonia-confirmation MESHD in Wuhan has delayed the growth and reduced size of the COVID-19 MESHD epidemic, decreased the peak number of the hospitalized cases by 96% in Wuhan. Our modeling also indicates that the earliest start date of COVID-19 MESHD in Wuhan may be Nov 2, 2019.

    Artificial intelligence-based CT metrics in relation with clinical outcome of COVID-19 MESHD in young and middle-aged adults

    Authors: Sihui Zeng; Weihong Liu; Xudong Yu; Yanli Li; Jiao Gao; Jiawei Li; Hanhui Li; Liang Mao; Chuanmiao Xie; Jianye Liang

    doi:10.21203/rs.3.rs-24561/v1 Date: 2020-04-22 Source: ResearchSquare

    Purposes: Currently, most researchers mainly analyzed COVID-19 MESHD pneumonia visually MESHD or qualitatively, probably somewhat time-consuming and not precise enough. This study aimed to excavate more information, such as differences in distribution, density, and severity of pneumonia lesions MESHD between males and females in a specific age group using artificial intelligence (AI)-based CT metrics. Besides, these metrics were incorporated into a clinical regression model to predict the short-term outcome.Methods: The clinical, laboratory information and a series of HRCT images from 49 patients, aged from 20 to 50 years and confirmed with COVID-19 MESHD, were collected. The volumes and percentages of infection (POI) among bilateral lungs and each bronchopulmonary segment were extracted using uAI-Discover- NCP PROTEIN software (version R001). The POI in three HU ranges, (i.e. <-300, -300~49 and ≥50 HU representing ground-glass opacity (GGO), mixed opacity and consolidation), were also extracted. Hospital stay was predicted with several POIs after adjusting days from illness onset to admission, leucocytes, lymphocytes, c-reactive protein HGNC, age and gender using a multiple linear regression model.Results: Right lower lobes had the highest POI, followed by left lower lobes, right upper lobes, middle lobes MESHD and left upper lobes. The distributions in lung lobes and segments were different between the sexes. Men had a higher total POI and GGO of the lungs, but less consolidation than women in initial CT (all p<0.05). The total POI, percentage of consolidation on initial CT and changed POI were positively correlated with hospital stay in the model.Conclusion: Both men and women had characteristic distributions in lung lobes MESHD and bronchopulmonary segments. AI-based CT quantitative metrics can provide more precise information regarding lesion distribution and severity to predict clinical outcome.

    Acute eosinophilic pneumonia associated with elevated NKT cell response in COVID-19 MESHD patients

    Authors: Dong-Min Kim; Jun-Won Seo; Yuri Kim; Uni Park; Na-Young Ha; Hyoree Park; Na Ra Yun; Da Young Kim; Sung Ho Yoon; Yong Sub Na; Do Sik Moon; Sung-Chul Lim; Choon-Mee Kim; Kyeongseok Jeon; Jun-Gu Kang; Yeon-Sook Kim; Nam-Hyuk Cho

    doi:10.21203/rs.3.rs-23607/v1 Date: 2020-04-17 Source: ResearchSquare

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2)1 and often results in fatal pneumonia MESHD.2,3 Despite the worldwide effect of the COVID-19 pandemic MESHD, the underlying mechanisms of the fatal viral pneumonia MESHD remain elusive. Here, we investigated respiratory specimens, including broncholoalveolar lavage fluids (BALFs) and bloods collected from three confirmed cases of COVID-19 MESHD patients with varying degrees of disease severity. Surprisingly, over 35% of cells from BALFs obtained from two pneumonic patients was comprised of eosinophils, while 20% was comprised of lymphocytes. Cytological analysis of sputa and tracheal aspirates from all three patients also revealed that more than 90% of total cells were eosinophils. Infiltration of CD16 HGNC+/ CD24 HGNC+ polymorphonuclear cells into lungs, together with elevated NKT cells in BALFs and peripheral blood samples, in patients with severe pneumonia MESHD was confirmed by flow cytometry. Moreover, rapid and profound IgE HGNC responses against the N protein PROTEIN of SARS-CoV-2 was only detected in plasma from a patient suffering from more severe and prolonged pneumonia MESHD. A significant reduction in oxygen demand with improved chest imaging was observed in two severe COVID-19 MESHD patients after treatment with a steroid, methylprednisolone. The present study provides evidence that acute eosinophilic MESHD pneumonia4 is associated with COVID-19 MESHD

    Prediction of SARS-CoV interaction with host proteins during lung aging reveals a potential role for TRIB3 HGNC in COVID-19 MESHD.

    Authors: Diogo de Moraes; Brunno Vivone Buquete Paiva; Sarah Santiloni Cury; Joao Pessoa Araujo Jr.; Marcelo Alves da Silva Mori; Robson Francisco Carvalho

    doi:10.1101/2020.04.07.030767 Date: 2020-04-09 Source: bioRxiv

    COVID-19 MESHD is prevalent in the elderly. Old individuals are more likely to develop pneumonia MESHD and respiratory failure MESHD due to alveolar damage MESHD, suggesting that lung senescence may increase the susceptibility to SARS-CoV-2 infection MESHD and replication. Considering that human coronavirus (HCoVs; SARS-CoV-2 and SARS-CoV) require host cellular factors for infection and replication, we analyzed Genotype-Tissue Expression (GTEx) data to test whether lung aging is associated with transcriptional changes in human protein-coding genes that potentially interact with these viruses. We found decreased expression of the gene tribbles homolog 3 ( TRIB3 HGNC) during aging in male individuals, and its protein was predicted to interact with HCoVs nucleocapsid protein PROTEIN and RNA-dependent RNA polymerase PROTEIN. Using publicly available lung single-cell data, we found TRIB3 HGNC expressed mainly in alveolar MESHD epithelial cells that express SARS-CoV-2 receptor ACE2 HGNC. Functional enrichment analysis of age-related genes, in common with SARS-CoV-induced perturbations, revealed genes associated with the mitotic cell cycle and surfactant metabolism. Given that TRIB3 HGNC was previously reported to decrease virus infection MESHD and replication, the decreased expression of TRIB3 HGNC in aged lungs may help explain why older male patients are related to more severe cases of the COVID-19 MESHD. Thus, drugs that stimulate TRIB3 HGNC expression should be evaluated as a potential therapy for the disease.

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MeSH Disease
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SARS-CoV-2 Proteins


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