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Na Zhu

Bio: Na Zhu is a academic researcher from Chinese Center for Disease Control and Prevention. The author has contributed to research in topic(s): Coronavirus & Virus. The author has an hindex of 12, co-authored 15 publication(s) receiving 23876 citation(s).

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Papers
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Open accessJournal ArticleDOI: 10.1056/NEJMOA2001017
Na Zhu1, Dingyu Zhang, Wenling Wang1, Xingwang Li2  +15 moreInstitutions (3)
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).

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Topics: Coronavirus (57%), Betacoronavirus (56%)

15,285 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30251-8
Roujian Lu1, Xiang Zhao1, Juan Li2, Peihua Niu1  +33 moreInstitutions (6)
22 Feb 2020-The Lancet
Abstract: Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

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Topics: Betacoronavirus (59%), Coronavirus (58%)

7,249 Citations


Open accessJournal ArticleDOI: 10.1038/S41586-020-2312-Y
Linlin Bao1, Wei Deng1, Baoying Huang2, Hong Gao1  +45 moreInstitutions (2)
07 May 2020-Nature
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern1. Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV)2. Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19. Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

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Topics: Coronavirus (60%), Virus (53%), Lung (51%) ...read more

617 Citations


Open accessJournal ArticleDOI: 10.1128/JVI.00023-19
Liang Shen1, Junwei Niu1, Chunhua Wang, Baoying Huang1  +7 moreInstitutions (2)
Abstract: Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection.IMPORTANCE Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.

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Topics: Coronavirus (53%)

164 Citations


Open accessPosted ContentDOI: 10.1101/2020.02.07.939389
Linlin Bao1, Wei Deng1, Baoying Huang2, Hong Gao1  +45 moreInstitutions (2)
11 Feb 2020-bioRxiv
Abstract: 2019-nCoV caused pneumonia cases in China has become a public health emergency of international concern (PHEIC). The first priority for prevention and treatment of the disease is to find the pathogenicity of 2019-nCoV in vivo. Weight loss and virus replication were detected in infected-hACE2 mice. The typical histopathology was interstitial pneumonia with significant inflammatory cells infiltration around the bronchioles and blood vessels, and viral antigens were observed in bronchial epithelial cells and alveolar epithelial cells. The phenomenon was not found in wild type mice infected with 2019-nCoV and the mock-infected hACE2 mice. The pathogenicity of 2019-nCoV in hACE2 mice was clarified and the Koch’s postulates was fulfilled as well, and the model may facilitate the development of therapeutics and vaccines against 2019-nCoV.

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  • Fig. 1 | Weight loss, virus replication and specific IgG production in hACE2 mice after infection with SARS-CoV-2. a, Weight loss was recorded for 14 days. hACE2 mice (n = 7) and wild-type (WT) mice (n = 3) were experimentally challenged intranasally with SARS-CoV-2 HB-01, and mock-treated hACE2 (ACE2 + mock) mice (n = 3) were used as control. According to two-tailed Mann–Whitney U-test, the weight of HB-01-infected hACE2 mice (ACE2 +  HB-01) displayed a significant decline compared with that of HB-01-infected wild-type mice (WT + HB-01) or mock-treated hACE2 mice (***P = 0.0005). b, To measure viral RNA, 12 mice were infected in each group. Three mice per group were killed, and their major organs (including testis in male mice) were collected for analysis of viral loads and virus titre at 1, 3, 5 and 7 dpi. The distribution of SARS-CoV-2 in the primary organs of HB-01-infected hACE2 mice was detected using RT–qPCR. c, Virus titres in the lungs were determined
    Fig. 1 | Weight loss, virus replication and specific IgG production in hACE2 mice after infection with SARS-CoV-2. a, Weight loss was recorded for 14 days. hACE2 mice (n = 7) and wild-type (WT) mice (n = 3) were experimentally challenged intranasally with SARS-CoV-2 HB-01, and mock-treated hACE2 (ACE2 + mock) mice (n = 3) were used as control. According to two-tailed Mann–Whitney U-test, the weight of HB-01-infected hACE2 mice (ACE2 +  HB-01) displayed a significant decline compared with that of HB-01-infected wild-type mice (WT + HB-01) or mock-treated hACE2 mice (***P = 0.0005). b, To measure viral RNA, 12 mice were infected in each group. Three mice per group were killed, and their major organs (including testis in male mice) were collected for analysis of viral loads and virus titre at 1, 3, 5 and 7 dpi. The distribution of SARS-CoV-2 in the primary organs of HB-01-infected hACE2 mice was detected using RT–qPCR. c, Virus titres in the lungs were determined

161 Citations


Cited by
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Open accessJournal ArticleDOI: 10.1056/NEJMOA2002032
Wei-jie Guan1, Zhengyi Ni1, Yu Hu1, Wenhua Liang1  +33 moreInstitutions (1)
Abstract: Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of...

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16,855 Citations


Open accessJournal ArticleDOI: 10.1001/JAMA.2020.1585
Dawei Wang1, Bo Hu1, Chang Hu1, Fangfang Zhu1  +10 moreInstitutions (1)
17 Mar 2020-JAMA
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

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Topics: Interquartile range (51%)

13,270 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2001316
Qun Li1, Xuhua Guan1, Peng Wu2, Xiaoye Wang1  +43 moreInstitutions (6)
Abstract: Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the...

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Topics: Coronavirus (54%)

10,234 Citations


Open accessJournal ArticleDOI: 10.1016/J.CELL.2020.02.052
16 Apr 2020-Cell
Abstract: The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Topics: Proteases (52%)

10,193 Citations


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30251-8
Roujian Lu1, Xiang Zhao1, Juan Li2, Peihua Niu1  +33 moreInstitutions (6)
22 Feb 2020-The Lancet
Abstract: Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

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Topics: Betacoronavirus (59%), Coronavirus (58%)

7,249 Citations


Performance
Metrics

Author's H-index: 12

No. of papers from the Author in previous years
YearPapers
20211
20206
20191
20163
20152
20131

Top Attributes

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Author's top 5 most impactful journals

PLOS ONE

2 papers, 80 citations

bioRxiv

2 papers, 192 citations

Nature Communications

2 papers, 129 citations

Nature

1 papers, 617 citations

Scientific Reports

1 papers, 95 citations

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