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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (2227)

ProteinN (575)

NSP5 (418)

ComplexRdRp (253)

ProteinE (148)


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SARS-CoV-2 Proteins
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    Cryo-EM structures of HKU2 and SADS-CoV spike glycoproteins PROTEIN and insights into coronavirus evolution

    Authors: Jinfang Yu; Shuyuan Qiao; Runyu Guo; Xinquan Wang

    doi:10.1101/2020.02.23.961912 Date: 2020-02-24 Source: bioRxiv

    A new porcine coronavirus SADS-CoV MESHD was recently identified from suckling piglets with severe diarrhea MESHD in southern China and its genome sequence is most identical (~95% identity) to that of bat -coronavirus HKU2. It again indicates bats are the natural reservoir of many coronaviruses that have great potential for cross-species transmission to animals and humans by recombination and/or mutation. Here we report the cryo-EM structures of HKU2 and SADS-CoV spike MESHD spike glycoprotein PROTEIN trimers at 2.38 [A] and 2.83 [A] resolution, respectively. HKU2 and SADS-CoV spikes MESHD exhibit very high structural similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 subunit responsible for cell attachment and receptor binding. We systematically analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and the S2 subunit of HKU2 spike with those of -, {beta}-, {gamma}-, and {delta}-coronavirus spikes. The results show that the NTD MESHD and CTD of HKU2/SADS-CoV are probably the most ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV S2 subunit also adopts a conformation distinct from other coronaviruses. These results structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV and {beta}-coronavirus spikes and provide new insights into the evolution and cross-species transmission of coronaviruses.

    COVID-19 MESHD Spike-host cell receptor GRP78 HGNC binding site prediction

    Authors: Ibrahim Ibrahim; Doaa Abdelmalek; Mohamed Elshahat; Abdo Elfiky

    doi:10.21203/rs.2.24599/v1 Date: 2020-02-24 Source: ResearchSquare

    Coronaviruses have been circulating between animals and humans repeatedly. A novel human coronavirus, named COVID-19 MESHD, has recently emerged in Hubei Province, China. Within the first two months, more than 2200 deaths have been confirmed, and there have been more than 79,000 hospitalized patients, mainly in China. Understanding the virus mode of host cell recognition may help to fight the disease and save lives. The spike protein PROTEIN of coronaviruses is the main driving force for host cell recognition. In this study, the COVID-19 MESHD corona viral spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The cyclic peptide Pep42 (CTVALPGGYVRVC) was reported earlier to be the docking platform of GRP78 in cancer MESHD cells. The COVID-19 MESHD spike protein PROTEIN is modeled using its counterpart, the SARS spike. Sequence and structural alignments show that four regions, in addition to its cyclic nature (the S-S bond), have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein PROTEIN in recognition of the host cell receptor. We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein PROTEIN model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues (region IV) of the spike can be used to develop therapeutics specific against COVID-19 MESHD.

    Rapid Detection of Novel Coronavirus ( COVID-19 MESHD) by Reverse Transcription-Loop-Mediated Isothermal Amplification

    Authors: Laura E Lamb; Sarah N Bartolone; Elijah Ward; Michael B Chancellor

    doi:10.1101/2020.02.19.20025155 Date: 2020-02-24 Source: medRxiv

    Novel Corona virus ( COVID-19 MESHD or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 MESHD detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT- LAMP HGNC) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 MESHD nucleic sequence. The samples were tested using RT- LAMP HGNC as well as by conventional qRT-PCR. Specificity of the RT- LAMP HGNC was evaluated by also testing against other related coronaviruses. RT- LAMP HGNC specifically detected COVID-19 MESHD in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.

    SARS-CoV-2 May Persist in Digestive Tract Longer than Respiratory Tract

    Authors: Yilin Hu; Lisha SHEN; Zheming XU; Jianying Zhou; Hua Zhou

    id:10.20944/preprints202002.0354.v1 Date: 2020-02-24 Source: Preprints.org

    Covid-19 MESHD has now become a public health concern worldwide. The infection primarily involves the respiratory tract. Hitherto, some Covid-19 MESHD pneumonia MESHD patients carry the viral nucleic acids, and the active virus was detected in stool specimens. The virus discharged with feces is a potential contagious source. In the present study, three Covid-19 MESHD respiratory tract infection MESHD patients showed no gastrointestinal symptoms, and two were positive for viral nucleic acids in anal swab specimens remained positive 6 and at least 14 days after virus turned negative in the respiratory tract, respectively (details of the patients were listed in Fig 1). Thus, for Covid-19 MESHD-infected patients with or without gastrointestinal symptoms MESHD, viral nucleic acids in stool specimens or anal swab specimens should be focused on for testing in order to decide the isolation duration of the patient.

    Rapid colorimetric detection of COVID-19 MESHD coronavirus using a reverse tran-scriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic plat-form: iLACO

    Authors: Lin Yu; Shanshan Wu; Xiaowen Hao; Xuelong Li; Xiyang Liu; Shenglong Ye; Heng Han; Xue Dong; Xin Li; Jiyao Li; Jianmin Liu; Na Liu; Wanzhong Zhang; Vicent Pelechano; Wei-Hua Chen; Xiushan Yin

    doi:10.1101/2020.02.20.20025874 Date: 2020-02-24 Source: medRxiv

    The recent outbreak of a novel coronavirus SARS-CoV-2 MESHD (also known as 2019-nCoV) threatens global health, given serious cause for concern. SARS-CoV-2 is a human-to-human pathogen that caused fever MESHD, severe respiratory disease MESHD and pneumonia MESHD (known as COVID-19 MESHD). By press time, more than 70,000 infected people had been confirmed worldwide. SARS-CoV-2 is very similar to the severe acute respiratory syndrome MESHD (SARS) coronavirus broke out 17 years ago. However, it has increased transmissibility as compared with the SARS-CoV, e.g. very often infected individuals without any symptoms could still transfer the virus to others. It is thus urgent to develop a rapid, accurate and onsite diagnosis methods in order to effectively identify these early infects MESHD, treat them on time and control the disease spreading. Here we developed an isothermal LAMP based method-iLACO (isothermal LAMP based method for COVID-19 MESHD) to amplify a fragment of the ORF1ab PROTEIN gene using 6 primers. We assured the species-specificity of iLACO by comparing the sequences of 11 related viruses by BLAST (including 7 similar coronaviruses, 2 influenza viruses and 2 normal coronaviruses). The sensitivity is comparable to Taqman based qPCR detection method, detecting synthesized RNA equivalent to 10 copies of 2019-nCoV virus. Reaction time varied from 15-40 minutes, depending on the loading of virus in the collected samples. The accuracy, simplicity and versatility of the new developed method suggests that iLACO assays can be conveniently applied with for 2019-nCoV threat control, even in those cases where specialized molecular biology equipment is not available.

    Estimating the risk of 2019 Novel Coronavirus death during the course of the outbreak in China, 2020

    Authors: Kenji Mizumoto; Gerardo Chowell

    doi:10.1101/2020.02.19.20025163 Date: 2020-02-23 Source: medRxiv

    Since the first case of Novel Coronavirus (2019-nCov) was identified in December 2019 in Wuhan City, China, the number of cases continues to grow across China and multiple cases have been exported to other countries. The cumulative number of reported deaths MESHD is at 637 as of February 7, 2020. Here we statistically estimated the time-delay adjusted death risk for Wuhan as well as for China excluding Wuhan to interpret the current severity of the epidemic in China. We found that the latest estimates of the death risk in Wuhan could be as high as 20% in the epicenter of the epidemic whereas we estimate it ~1% in the relatively mildly-affected areas. Because the elevated death risk estimates are likely associated with a breakdown of the medical/health system, enhanced public health interventions including social distancing and movement restrictions should be effectively implemented to bring the epidemic under control.

    Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study

    Authors: Juanjuan Zhang; Maria Litvinova; Wei Wang; Yan Wang; Xiaowei Deng; Xinghui Chen; Mei Li; Wen Zheng; Lan Yi; Xinhua Chen; Qianhui Wu; Yuxia Liang; Xiling Wang; Juan Yang; Kaiyuan Sun; Ira M. Longini Jr.; M. Elizabeth Halloran; Peng Wu; Benjamin J. Cowling; Stefano Merler; Cecile Viboud; Alessandro Vespignani; Marco Ajelli; Hongjie Yu

    doi:10.1101/2020.02.21.20026328 Date: 2020-02-23 Source: medRxiv

    Background The COVID-19 MESHD epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy. Methods We collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level. Results The median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January. Conclusion Our findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 MESHD transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.

    Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China

    Authors: Mingli Yuan; Wen Yin; Zhaowu Tao; Weijun Tan; Yi Hu

    doi:10.1101/2020.02.22.20024927 Date: 2020-02-23 Source: medRxiv

    Radiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia MESHD (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis. We retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated. 27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality. 2019-nCoV was more likely to infect MESHD elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.

    The efficacy of convalescent plasma for the treatment of severe influenza

    Authors: Zhiheng Xu; Jianmeng Zhou; Yongbo Huang; Xuesong Liu; Yonghao Xu; Sibei Chen; Dongdong Liu; Zhimin Lin; Xiaoqing Liu; Yimin Li

    doi:10.1101/2020.02.20.20025593 Date: 2020-02-23 Source: medRxiv

    Background. Administration of convalescent plasma may be of clinical benefit for treatment of severe acute viral respiratory infections MESHD. However, no clear evidence exists to support or oppose convalescent plasma use in clinical practice. We conducted a systematic review and meta-analysis to assess the evidence of randomized controlled trials (RCTs) in the convalescent plasma for the treatment of severe influenza. Methods. Healthcare databases were searched in February 2020. All records were screened against the eligibility criteria. Data extraction and risk of bias assessments were undertaken. The primary outcome was case fatality rates by influenza. Results. We identified 5 RCTs of severe influenza. The pooled analyses showed no evidence for a reduction in mortality (Odds Ratio (OR) 1.06; p = 0.87; I2 = 35%). We also found non significant reductions in days in ICU and hospital, and days on mechanical ventilation. There seemed to have a biological benefit of increasing HAI titer levels and decreasing influenza B virus loads and cytokines after convalescent plasma treatment. No serious adverse events was reported between two groups. Studies were commonly of low risk of bias with high quality. Conclusions. Convalescent plasma appears safe but may not reduce mortality in severe influenza. This therapy should be studied within the context of a well designed clinical trial for treatment of SARS Cov 2 infection.

    Evaluating the impact of international airline suspensions on COVID-19 MESHD direct importation risk

    Authors: Aniruddha Adiga; Srinivasan Venkatramanan; James Schlitt; Akhil Peddireddy; Allan Dickerman; Andrei Bura; Andrew Warren; Brian D Klahn; Chunhong Mao; Dawen Xie; Dustin Machi; Erin Raymond; Fanchao Meng; Golda Barrow; Henning Mortveit; Jiangzhuo Chen; Jim Walke; Joshua Goldstein; Mandy L Wilson; Mark Orr; Przemyslaw Porebski; Pyrros A Telionis; Richard Beckman; Stefan Hoops; Stephen Eubank; Young Yun Baek; Bryan Lewis; Madhav Marathe; Chris Barrett

    doi:10.1101/2020.02.20.20025882 Date: 2020-02-23 Source: medRxiv

    Global airline networks play a key role in the global importation of emerging infectious diseases MESHD. Detailed information on air traffic between international airports has been demonstrated to be useful in retrospectively validating and prospectively predicting case emergence in other countries. In this paper, we use a well-established metric known as effective distance on the global air traffic data from IATA to quantify risk of emergence for different countries as a consequence of direct importation from China, and compare it against arrival times for the first 24 countries. Using this model trained on official first reports from WHO, we estimate time of arrival (ToA) for all other countries. We then incorporate data on airline suspensions to recompute the effective distance and assess the effect of such cancellations in delaying the estimated arrival time for all other countries. Finally we use the infectious disease vulnerability indices to explain some of the estimated reporting delays.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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