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CHLOROQUINE HYPE DERAILS CORONAVIRUS DRUG TRIALS 期刊论文
NATURE, 2020, 580 (7805) : 573-573
作者:  Hu, Minjie;  Zheng, Xiaobin;  Fan, Chen-Ming;  Zheng, Yixian
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

With politicians touting the potential benefits of malaria drugs to fight COVID-19, some people are turning away from clinical trials of other therapies.


With politicians touting the potential benefits of malaria drugs to fight COVID-19, some people are turning away from clinical trials of other therapies.


  
OPEN SCIENCE TAKES ON COVID-19 期刊论文
NATURE, 2020, 581 (7806) : 109-110
作者:  Mudelsee, Manfred;  Borngen, Michael;  Tetzlaff, Gerd;  Grunewald, Uwe
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Data sharing, open-source designs for medical equipment, and hobbyists are all being harnessed to combat COVID-19.


Data sharing, open-source designs for medical equipment, and hobbyists are all being harnessed to combat COVID-19.


  
Population flow drives spatio-temporal distribution of COVID-19 in China 期刊论文
NATURE, 2020
作者:  Fernandez, Diego Carlos;  Komal, Ruchi;  Langel, Jennifer;  Ma, Jun;  Duy, Phan Q.;  Penzo, Mario A.;  Zhao, Haiqing;  Hattar, Samer
收藏  |  浏览/下载:69/0  |  提交时间:2020/07/03

Sudden, large-scale and diffuse human migration can amplify localized outbreaks of disease into widespread epidemics(1-4). Rapid and accurate tracking of aggregate population flows may therefore be epidemiologically informative. Here we use 11,478,484 counts of mobile phone data from individuals leaving or transiting through the prefecture of Wuhan between 1 January and 24 January 2020 as they moved to 296 prefectures throughout mainland China. First, we document the efficacy of quarantine in ceasing movement. Second, we show that the distribution of population outflow from Wuhan accurately predicts the relative frequency and geographical distribution of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) until 19 February 2020, across mainland China. Third, we develop a spatio-temporal '  risk source'  model that leverages population flow data (which operationalize the risk that emanates from epidemic epicentres) not only to forecast the distribution of confirmed cases, but also to identify regions that have a high risk of transmission at an early stage. Fourth, we use this risk source model to statistically derive the geographical spread of COVID-19 and the growth pattern based on the population outflow from Wuhan  the model yields a benchmark trend and an index for assessing the risk of community transmission of COVID-19 over time for different locations. This approach can be used by policy-makers in any nation with available data to make rapid and accurate risk assessments and to plan the allocation of limited resources ahead of ongoing outbreaks.


Modelling of population flows in China enables the forecasting of the distribution of confirmed cases of COVID-19 and the identification of areas at high risk of SARS-CoV-2 transmission at an early stage.


  
Massively multiplexed nucleic acid detection with Cas13 期刊论文
NATURE, 2020, 582 (7811) : 277-+
作者:  Mahato, Biraj;  Kaya, Koray Dogan;  Fan, Yan;  Sumien, Nathalie;  Shetty, Ritu A.;  Zhang, Wei;  Davis, Delaney;  Mock, Thomas;  Batabyal, Subrata;  Ni, Aiguo;  Mohanty, Samarendra;  Han, Zongchao;  Farjo, Rafal;  Forster, Michael J.;  Swaroop, Anand;  Chavala, Sai H.
收藏  |  浏览/下载:62/0  |  提交时间:2020/07/03

CRISPR-based nucleic acid detection is used in a platform that can simultaneously detect 169 human-associated viruses in multiple samples, providing scalable, multiplexed pathogen detection aimed at routine surveillance for public health.


The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples(1-3)while simultaneously testing for many pathogens(4-6). Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents(7)self-organize in a microwell array(8)to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health(9-11).


  
The online competition between pro- and anti-vaccination views 期刊论文
NATURE, 2020, 582 (7811) : 230-+
作者:  Wu, Fan;  Zhao, Su;  Yu, Bin;  Chen, Yan-Mei;  Wang, Wen;  Song, Zhi-Gang;  Hu, Yi;  Tao, Zhao-Wu;  Tian, Jun-Hua;  Pei, Yuan-Yuan;  Yuan, Ming-Li;  Zhang, Yu-Ling;  Dai, Fa-Hui;  Liu, Yi;  Wang, Qi-Min;  Zheng, Jiao-Jiao;  Xu, Lin;  Holmes, Edward C.;  Zhang, Yong-Zhen
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.


Distrust in scientific expertise(1-14) is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks(2-4), as happened for measles in 2019(5,6). Homemade remedies(7,8) and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice(9-11). There is a lack of understanding about how this distrust evolves at the system level(13,14). Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change(11), and highlight the key role of network cluster dynamics in multi-species ecologies(15).


  
Coronavirus blood-clot mystery intensifies 期刊论文
NATURE, 2020, 581 (7808) : 250-250
作者:  DeWeerdt, Sarah
收藏  |  浏览/下载:0/0  |  提交时间:2020/07/03

Research begins to pick apart the mechanisms behind a deadly COVID-19 complication.


Research begins to pick apart the mechanisms behind a deadly COVID-19 complication.


  
Structure of M-pro from SARS-CoV-2 and discovery of its inhibitors 期刊论文
NATURE, 2020, 582 (7811) : 289-+
作者:  Li, Nan;  Jasanoff, Alan
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.


A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019-2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)(1-4). Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (M-pro) of SARS-CoV-2: M-pro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-2(5,6). We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of M-pro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds-including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds-as inhibitors of M-pro. Six of these compounds inhibited M-pro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 mu M. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available.


  
Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals 期刊论文
NATURE, 2020
作者:  Grishin, Evgeni;  Malamud, Uri;  Perets, Hagai B.;  Wandel, Oliver;  Schaefer, Christoph M.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood(1-3). Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding  this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions  however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.


Aerodynamic analysis of SARS-CoV-2 RNA in two hospitals in Wuhan indicates that SARS-CoV-2 may have the potential to be transmitted through aerosols, although the infectivity of the virus RNA was not established in this study.


  
Without food, there can be no exit from the pandemic 期刊论文
NATURE, 2020, 580 (7805) : 588-589
作者:  Citron, Y. Rose;  Zoncu, Roberto
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

Countries must join forces to avert a global food crisis from COVID-19.


Countries must join forces to avert a global food crisis from COVID-19.


  
Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform 期刊论文
NATURE, 2020
作者:  Touat, Mehdi;  Li, Yvonne Y.;  Boynton, Adam N.;  Spurr, Liam F.;  Iorgulescu, J. Bryan;  Bohrson, Craig L.;  Cortes-Ciriano, Isidro;  Birzu, Cristina;  Geduldig, Jack E.;  Pelton, Kristine;  Lim-Fat, Mary Jane;  Pal, Sangita;  Ferrer-Luna, Ruben;  Ramkissoon, Shakti H.;  Dubois, Frank;  Bellamy, Charlotte;  Currimjee, Naomi;  Bonardi, Juliana;  Qian Kenin;  Ho, Patricia;  Malinowski, Seth;  Taquet, Leon;  Jones, Robert E.;  Shetty, Aniket;  Chow, Kin-Hoe;  Sharaf, Radwa;  Pavlick, Dean;  Albacker, Lee A.;  Younan, Nadia;  Baldini, Capucine;  Verreault, Maite;  Giry, Marine;  Guillerm, Erell;  Ammari, Samy;  Beuvon, Frederic;  Mokhtari, Karima;  Alentorn, Agusti;  Dehais, Caroline;  Houillier, Caroline;  Laigle-Donadey, Florence;  Psimaras, Dimitri;  Lee, Eudocia Q.;  Nayak, Lakshmi;  McFaline-Figueroa, J. Ricardo;  Carpentier, Alexandre;  Cornu, Philippe;  Capelle, Laurent;  Mathon, Bertrand;  Barnholtz-Sloan, Jill S.;  Chakravarti, Arnab;  Bi, Wenya Linda;  Chiocca, E. Antonio;  Fehnel, Katie Pricola;  Alexandrescu, Sanda;  Chi, Susan N.;  Haas-Kogan, Daphne;  Batchelor, Tracy T.;  Frampton, Garrett M.;  Alexander, Brian M.;  Huang, Raymond Y.;  Ligon, Azra H.;  Coulet, Florence;  Delattre, Jean-Yves;  Hoang-Xuan, Khe;  Meredith, David M.;  Santagata, Sandro;  Duval, Alex;  Sanson, Marc;  Cherniack, Andrew D.;  Wen, Patrick Y.;  Reardon, David A.;  Marabelle, Aurelien;  Park, Peter J.;  Idbaih, Ahmed;  Beroukhim, Rameen;  Bandopadhayay, Pratiti;  Bielle, Franck;  Ligon, Keith L.
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Reverse genetics has been an indispensable tool to gain insights into viral pathogenesis and vaccine development. The genomes of large RNA viruses, such as those from coronaviruses, are cumbersome to clone and manipulate inEscherichia coliowing to the size and occasional instability of the genome(1-3). Therefore, an alternative rapid and robust reverse-genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform to genetically reconstruct diverse RNA viruses, including members of theCoronaviridae,FlaviviridaeandPneumoviridaefamilies. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples or synthetic DNA, and these fragments were then reassembled in one step inSaccharomyces cerevisiaeusing transformation-associated recombination cloning to maintain the genome as a yeast artificial chromosome. T7 RNA polymerase was then used to generate infectious RNA to rescue viable virus. Using this platform, we were able to engineer and generate chemically synthesized clones of the virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(4), which has caused the recent pandemic of coronavirus disease (COVID-19), in only a week after receipt of the synthetic DNA fragments. The technical advance that we describe here facilitates rapid responses to emerging viruses as it enables the real-time generation and functional characterization of evolving RNA virus variants during an outbreak.


A yeast-based synthetic genomics platform is used to reconstruct and characterize large RNA viruses from synthetic DNA fragments  this technique will facilitate the rapid analysis of RNA viruses, such as SARS-CoV-2, during an outbreak.