Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (654)

ProteinN (149)

NSP5 (75)

ComplexRdRp (46)

ProteinE (43)


SARS-CoV-2 Proteins
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    Analysis of the epidemic growth of the early 2019-nCoV outbreak using internationally confirmed cases

    Authors: Qingyuan Zhao; Yang Chen; Dylan S Small

    doi:10.1101/2020.02.06.20020941 Date: 2020-02-09 Source: medRxiv

    Background: On January 23, 2020, a quarantine was imposed on travel in and out of Wuhan, where the 2019 novel coronavirus (2019-nCoV) outbreak originated from. Previous analyses estimated the basic epidemiological parameters using symptom onset dates of the confirmed cases in Wuhan and outside China. Methods: We obtained information on the 46 coronavirus cases who traveled from Wuhan before January 23 and have been subsequently confirmed in Hong Kong, Japan, Korea, Macau, Singapore, and Taiwan as of February 5, 2020. Most cases have detailed travel history and disease progress. Compared to previous analyses, an important distinction is that we used this data to informatively simulate the infection time of each case using the symptom onset time, previously reported incubation interval, and travel history. We then fitted a simple exponential growth model with adjustment for the January 23 travel ban to the distribution of the simulated infection time. We used a Bayesian analysis with diffuse priors to quantify the uncertainty of the estimated epidemiological parameters. We performed sensitivity analysis to different choices of incubation interval and the hyperparameters in the prior specification. Results: We found that our model provides good fit to the distribution of the infection time. Assuming the travel rate to the selected countries and regions is constant over the study period, we found that the epidemic was doubling in size every 2.9 days (95% credible interval [CrI], 2 days--4.1 days). Using previously reported serial interval for 2019-nCoV, the estimated basic reproduction number is 5.7 (95% CrI, 3.4--9.2). The estimates did not change substantially if we assumed the travel rate doubled in the last 3 days before January 23, when we used previously reported incubation interval for severe acute respiratory syndrome MESHD (SARS), or when we changed the hyperparameters in our prior specification. Conclusions: Our estimated epidemiological parameters are higher than an earlier report using confirmed cases in Wuhan. This indicates the 2019-nCoV could have been spreading faster than previous estimates.

    ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism

    Authors: Jun Wang; Shanmeizi Zhao; Ming Liu; Zhiyao Zhao; Yiping Xu; Ping Wang; Meng Lin; Yanhui Xu; Bing Huang; Xiaoyu Zuo; Zhanghua Chen; Fan Bai; Jun Cui; Andrew M Lew; Jincun Zhao; Yan Zhang; Haibin Luo; Yuxia Zhang

    doi:10.1101/2020.02.05.20020545 Date: 2020-02-07 Source: medRxiv

    Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia MESHD first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV MESHD and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike MESHD spike protein PROTEIN induced lung injury MESHD by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation MESHD by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis MESHD or inflammatory bowel disease MESHD ( IBD MESHD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection MESHD, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection MESHD.

    Network-based Drug Repurposing for Human Coronavirus

    Authors: Yadi Zhou; Yuan Hou; Jiayu Shen; Yin Huang; William Martin; Feixiong Cheng

    doi:10.1101/2020.02.03.20020263 Date: 2020-02-05 Source: medRxiv

    Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV) MESHD, and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV MESHD (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins PROTEIN of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV MESHD. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.

    Human-to-human transmission of 2019-novel coronavirus (2019-nCoV)

    Authors: Min Kang; Jie Wu; Wenjun Ma; Jianfeng He; Jing Lu; Tao Liu; Baisheng Li; Shujiang Mei; Feng Ruan; Lifeng Lin; Lirong Zou; Changwen Ke; Haojie Zhong; Yingtao Zhang; Xuguang Chen; Zhe Liu; Qi Zhu; Jianpeng Xiao; Jianxiang Yu; Jianxiong Hu; Weilin Zeng; Xing Li; Yuhuang Liao; Xiujuan Tang; Songjian Xiao; Ying Wang; Yingchao Song; Xue Zhuang; Lijun Liang; Siqing Zeng; Guanhao He; Peng Lin; Huihong Deng; Tie Song

    doi:10.1101/2020.02.03.20019141 Date: 2020-02-05 Source: medRxiv

    Background: On December 31, 2019, an outbreak of COVID-19 MESHD in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 MESHD case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid MESHD ( BALF MESHD), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections MESHD. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections MESHD. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections MESHD were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV MESHD-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections MESHD, community and nosocomial infections MESHD were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.

    Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV

    Authors: Xiang He; Lei Zhang; Qin Ran; Anying Xiong; Junyi Wang; Dehong Wu; Feng Chen; Guoping Li

    doi:10.1101/2020.02.03.20020206 Date: 2020-02-05 Source: medRxiv

    The 2019-nCoV is reported to share the same entry ( ACE2 HGNC) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 HGNC in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility, which was consistent with current clinical observations. Moreover, based on the expression of ACE2 HGNC in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 HGNC in SARS-CoV infected MESHD cells suggested that ACE2 HGNC was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. We also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings could explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.

    Preliminary identification of potential vaccine targets for 2019-nCoV based on SARS-CoV immunological studies

    Authors: Syed Faraz Ahmed; Ahmed A. Quadeer; Matthew R. McKay

    doi:10.1101/2020.02.03.933226 Date: 2020-02-04 Source: bioRxiv

    The beginning of 2020 has seen the emergence of COVID-19 MESHD outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV MESHD, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV MESHD. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV MESHD, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins PROTEIN that map identically to SARS-CoV-2 proteins MESHD. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

    Specific ACE2 HGNC Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection MESHD

    Authors: Xiaoqiang Chai; Longfei Hu; Yan Zhang; Weiyu Han; Zhou Lu; Aiwu Ke; Jian Zhou; Guoming Shi; Nan Fang; Jia Fan; Jiabin Cai; Jue Fan; Fei Lan

    doi:10.1101/2020.02.03.931766 Date: 2020-02-04 Source: bioRxiv

    A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2 HGNC, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS) MESHD, has recently been demonstrated in mediating 2019-nCoV infection MESHD. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage MESHD, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 HGNC in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 HGNC positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS MESHD and 2019-nCoV patients may not be due to hepatocyte damage MESHD, but cholangiocyte dysfunction MESHD and other causes such as drug induced and systemic inflammatory response induced liver injury MESHD. Our findings indicate that special care of liver dysfunction MESHD should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

    Machine intelligence design of 2019-nCoV drugs

    Authors: Duc Duy Nguyen; Kaifu Gao; Rui Wang; Guowei Wei

    doi:10.1101/2020.01.30.927889 Date: 2020-02-04 Source: bioRxiv

    Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV MESHD) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV MESHD are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.

    Potent neutralization of 2019 novel coronavirus by recombinant ACE2 HGNC-Ig

    Authors: Changhai Lei; Wenyan Fu; Kewen Qian; Tian Li; Sheng Zhang; Min Ding; Shi Hu

    doi:10.1101/2020.02.01.929976 Date: 2020-02-02 Source: bioRxiv

    2019-nCoV, which is a novel coronavirus emerged in Wuhan, China, at the end of 2019, has caused at least infected 11,844 as of Feb 1, 2020. However, there is no specific antiviral treatment or vaccine currently. Very recently report had suggested that novel CoV would use the same cell entry receptor, ACE2 HGNC, as the SARS-CoV MESHD. In this report, we generated a novel recombinant protein by connecting the extracellular domain of human ACE2 HGNC to the Fc region of the human immunoglobulin IgG1. An ACE2 HGNC mutant with low catalytic activity was also used in the study. The fusion proteins were then characterized. Both fusion proteins has high affinity binding to the receptor-binding domain (RBD) of SARS-CoV MESHD and 2019-nCoV and exerted desired pharmacological properties. Moreover, fusion proteins potently neutralized SARS-CoV MESHD and 2019-nCoV in vitro. As these fusion proteins exhibit cross-reactivity against coronaviruses, they could have potential applications for diagnosis, prophylaxis, and treatment of 2019-nCoV.

    Transmission and epidemiological characteristics of Novel Coronavirus (2019-nCoV)-Infected Pneumonia(NCIP):preliminary evidence obtained in comparison with 2003-SARS

    Authors: Rongqiang Zhang; Hui Liu; Fengying Li; Bei Zhang; Qiling Liu; Xiangwen Li; Limei Luo

    doi:10.1101/2020.01.30.20019836 Date: 2020-02-02 Source: medRxiv

    Objectives: Latest epidemic data of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected Pneumonia MESHD ( COVID-19 MESHD) was collected and a detailed statistical analysis was carried out to make comparison with 2003-SARS in order to provide scientific reference for the prevention and control of COVID-19 MESHD. Methods: The information of COVID-19 MESHD and 2003-SARS from websites of NHCPRC and the World Health Organization was collected, and then the transmission dynamics of the two kinds of infectious diseases MESHD were analyzed. The information of 853 confirmed COVID-19 MESHD patients obtained from the website of health committees of 18 provinces. A descriptive epidemiological analysis method was employed to carefully analyze the epidemic characteristics. Subsequently, the COVID-19 MESHD epidemic data in Wuhan and other inland regions of China was analyzed separately and compared. A multivariate function model was constructed based on the confirmed COVID-19 MESHD case data. Results: The growth rate of new cases and deaths of COVID-19 MESHD were significantly faster than those of 2003-SARS. The number of confirmed cases in Wuhan and other inland areas both showed increasing trends. 853 confirmed COVID-19 MESHD cases aged 1 months to 94 years and the average age was (45.05 {+/-} 17.22) years. The gender ratio (M: F) was 1.12: 1. Conclusions: The fatality rate of COVID-19 MESHD is lower than that of 2003-SARS and the cure rate is higher. The age of COVID-19 MESHD patients is mainly concentrated in the 30-50 years old (60.61%). The harm of the first-generation COVID-19 MESHD patients is higher than that of secondary cases.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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