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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 77,613 bioRxiv papers from 336,379 authors.

Most downloaded bioRxiv papers, since beginning of last month

75,929 results found. For more information, click each entry to expand.

101: Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)
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Posted to bioRxiv 21 Feb 2020

Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)
1,460 downloads microbiology

Jiahua He, Huanyu Tao, Yumeng Yan, Sheng-You Huang, Yi Xiao

Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019- nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

102: Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56 °C damages its genome integrity seriously
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Posted to bioRxiv 22 Feb 2020

Inactivating porcine coronavirus before nuclei acid isolation with the temperature higher than 56 °C damages its genome integrity seriously
1,447 downloads molecular biology

Qingxin Zhang, Qingshun Zhao

2019-Novel Coronavirus (2019-nCoV) is the pathogen of Corona Virus Disease 2019. Nucleic acid detection of 2019-nCoV is one of the key indicators for clinical diagnosis. However, the positive rate is only 30-50%. Currently, fluorescent quantitative RT-PCR technology is mainly used to detect 2019-nCoV. According to "The Laboratory Technical Guidelines for Detection 2019-nCoV (Fourth Edition)" issued by National Health and Commission of China and "The Experts' Consensus on Nucleic Acid Detection of 2019-nCoV" released by Chinese Society of Laboratory Medicine, the human samples must be placed under 56°C or higher to inactivate the viruses in order to keep the inspectors from virus infection before the nucleic acids were isolated as the template of qRT-PCR. In this study, we demonstrated that the virus inactivation treatment disrupts its genome integrity seriously when using porcine epidemic diarrhea virus (vaccine), a kind of coronavirus, as a model. Our results showed that only 50.11% of the detectable viral templates left after the inactivation of 56°C for 30 minutes and only 3.36% left after the inactivation of 92°C for 5 minutes when the samples were preserved by Hank's solution, one of an isotonic salt solutions currently suggested. However, the detectable templates of viral nucleic acids can be unchanged after the samples were incubated at 56°C or higher if the samples were preserved with an optimized solution to protect the RNA from being disrupted. We therefore highly recommend to carry out systematic investigation on the impact of high temperature inactivation on the integrity of 2019-nCoV genome and develop a sample preservation solution to protect the detectable templates of 2019-nCoV nucleic acids from high temperature inactivation damage.

103: Macrophages transfer mitochondria to neurons to resolve inflammatory pain
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Posted to bioRxiv 13 Feb 2020

Macrophages transfer mitochondria to neurons to resolve inflammatory pain
1,434 downloads neuroscience

Ramin Raoof, Michiel van der Vlist, Hanneke L.D.M. Willemen, Judith Prado, Sabine Versteeg, Martijn Vos, Roeland Lockhorst, R. Jeroen Pasterkamp, William Khoury-Hanold, Linde Meyaard, Niels Eijkelkamp

The current paradigm states that inflammatory pain passively resolves following the cessation of the inflammatory insult. Yet, in a substantial proportion of patients with inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, spontaneous or treatment-induced resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight as how inflammatory pain is resolved is lacking. Here we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. To resolve pain, macrophages transfer mitochondria to sensory neurons. This transfer requires expression of CD200 Receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain and suggests a new direction for treatment of chronic pain.

104: In-cell architecture of an actively transcribing-translating expressome
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Posted to bioRxiv 28 Feb 2020

In-cell architecture of an actively transcribing-translating expressome
1,433 downloads molecular biology

Francis J O’Reilly, Liang Xue, Andrea Graziadei, Ludwig Sinn, Swantje Lenz, Dimitry Tegunov, Cedric Blötz, Wim J. H. Hagen, Patrick Cramer, Jörg Stülke, Julia Mahamid, Juri Rappsilber

Structural biology performed inside cells can capture molecular machines in action within their native context. Here we develop an integrative in-cell structural approach using the genome-reduced human pathogen Mycoplasma pneumoniae. We combine whole-cell crosslinking mass spectrometry, cellular cryo-electron tomography, and integrative modeling to determine an in-cell architecture of a transcribing and translating expressome at sub-nanometer resolution. The expressome comprises RNA polymerase (RNAP), the ribosome, and the transcription elongation factors NusG and NusA. We pinpoint NusA at the interface between a NusG-bound elongating RNAP and the ribosome, and propose it could mediate transcription-translation coupling. Translation inhibition dissociates the expressome, whereas transcription inhibition stalls and rearranges it, demonstrating that the active expressome architecture requires both translation and transcription elongation within the cell.

105: The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2
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Posted to bioRxiv 17 Mar 2020

The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2
1,423 downloads biochemistry

Erik Procko

The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency, and no approved therapeutics or vaccines are currently available. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic and prophylactic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S at a cell surface. Mutations are found across the interface and also at buried sites where they are predicted to enhance folding and presentation of the interaction epitope. The N90-glycan on ACE2 hinders association. The mutational landscape offers a blueprint for engineering high affinity ACE2 receptors to meet this unprecedented challenge.

106: Retrospective identification of rare cell populations underlying drug resistance connects molecular variability with cell fate
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Posted to bioRxiv 19 Mar 2020

Retrospective identification of rare cell populations underlying drug resistance connects molecular variability with cell fate
1,418 downloads systems biology

Benjamin L. Emert, Christopher Coté, Eduardo A. Torre, Ian P Dardani, Connie L. Jiang, Naveen Jain, Sydney M. Shaffer, Arjun Raj

Molecular differences between individual cells can lead to dramatic differences in cell fate following an applied treatment, such as the difference between death versus survival of cancer cells upon receiving anti-cancer drugs. However, current strategies to retrospectively identify the cells that give rise to distinct rare behaviors and determine their distinguishing molecular characteristics remain limited. Here we describe Rewind, a methodology that combines genetic barcoding with an RNA-based readout to directly capture rare cells that give rise to cellular behaviors of interest, specifically the emergence of resistance to targeted cancer therapy. Using Rewind, we analyzed over 5 million cells to identify differences in gene expression and MAP-kinase signaling in single melanoma cells that mark a rare subpopulation of drug-naive cells (initial frequency of ~1:1000-1:10,000 cells) that ultimately gives rise to drug resistant clones. We further show that even within this rare subpopulation, molecular differences between single cells before the application of drug predict future differences in drug resistant behavior. Similarly, we show that treatments that modify the frequency of resistance can allow otherwise non-resistant cells in the drug-naive population to become resistant, and that these new populations are marked by the variable expression of distinct genes. Together, our results reveal the presence of cryptic variability that can underlie a range of distinct rare-cell phenotypic outcomes upon drug exposure. Applying Rewind to other rare biological phenomena, such as cancer metastasis, tissue regeneration, and stem cell reprogramming, may provide a means to map rare cellular states to the unique cellular fates to which they give rise.

107: Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies
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Posted to bioRxiv 04 Feb 2020

Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies
1,401 downloads bioinformatics

Syed Faraz Ahmed, Ahmed A. Quadeer, Matthew R. McKay

The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (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, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. 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.

108: Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
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Posted to bioRxiv 04 Feb 2020

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
1,391 downloads genomics

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

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

109: Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)
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Posted to bioRxiv 07 Mar 2020

Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)
1,382 downloads evolutionary biology

Bin Fang, Linlin Liu, Xiao Yu, Xiang Li, Guojun Ye, Juan Xu, Ling Zhang, Faxian Zhan, Guiming Liu, Tao Pan, Yilin Shu, Yongzhong Jiang

Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that the view, pangolin acted as an intermediate host, may be controversial. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximate 2 km), indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately concluded that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term and then leading to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019, which may indicated that the transmission could have begun from person to person in mid to late November.

110: Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia
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Posted to bioRxiv 05 Mar 2020

Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia
1,380 downloads microbiology

Jessica E Manning, Jennifer A Bohl, Sreyngim Lay, Sophana Chea, Ly Sovann, Yi Sengdoeurn, Seng Heng, Chan Vuthy, Katrina Kalantar, Vida Ahyong, Michelle Tan, Jonathan Sheu, Cristina M Tato, Joseph L. DeRisi, Laurence Baril, Veasna Duong, Philippe Dussart, Erik A. Karlsson

Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodia's first case of COVID-2019.

111: Glacier ice archives fifteen-thousand-year-old viruses
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Posted to bioRxiv 07 Jan 2020

Glacier ice archives fifteen-thousand-year-old viruses
1,353 downloads ecology

Zhi-Ping Zhong, Natalie E. Solonenko, Yueh-Fen Li, Maria C. Gazitúa, Simon Roux, Mary E. Davis, James L Van Etten, Ellen Mosley-Thompson, Virginia I Rich, Matthew B. Sullivan, Lonnie G. Thompson

While glacier ice cores provide climate information over tens to hundreds of thousands of years, study of microbes is challenged by ultra-low-biomass conditions, and virtually nothing is known about co-occurring viruses. Here we establish ultra-clean microbial and viral sampling procedures and apply them to two ice cores from the Guliya ice cap (northwestern Tibetan Plateau, China) to study these archived communities. This method reduced intentionally contaminating bacterial, viral, and free DNA to background levels in artificial-ice-core control experiments, and was then applied to two authentic ice cores to profile their microbes and viruses. The microbes differed significantly across the two ice cores, presumably representing the very different climate conditions at the time of deposition that is similar to findings in other cores. Separately, viral particle enrichment and ultra-low-input quantitative viral metagenomic sequencing from ~520 and ~15,000 years old ice revealed 33 viral populations (i.e., species-level designations) that represented four known genera and likely 28 novel viral genera (assessed by gene-sharing networks). In silico host predictions linked 18 of the 33 viral populations to co-occurring abundant bacteria, including Methylobacterium, Sphingomonas, and Janthinobacterium, indicating that viruses infected several abundant microbial groups. Depth-specific viral communities were observed, presumably reflecting differences in the environmental conditions among the ice samples at the time of deposition. Together, these experiments establish a clean procedure for studying microbial and viral communities in low-biomass glacier ice and provide baseline information for glacier viruses, some of which appear to be associated with the dominant microbes in these ecosystems.

112: The evolutionary history of Neandertal and Denisovan Y chromosomes
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Posted to bioRxiv 09 Mar 2020

The evolutionary history of Neandertal and Denisovan Y chromosomes
1,337 downloads evolutionary biology

Martin Petr, Mateja Hajdinjak, Qiaomei Fu, Elena Essel, Hélène Rougier, Isabelle Crevecoeur, Patrick Semal, Liubov V. Golovanova, Vladimir B. Doronichev, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Michael V. Shunkov, Maxim B. Kozlikin, Anatoli P. Derevianko, Benjamin Vernot, Matthias Meyer, Janet Kelso

Ancient DNA has allowed the study of various aspects of human history in unprecedented detail. However, because the majority of archaic human specimens preserved well enough for genome sequencing have been female, comprehensive studies of Y chromosomes of Denisovans and Neandertals have not yet been possible. Here we present sequences of the first Denisovan Y chromosomes (Denisova 4 and Denisova 8), as well as the Y chromosomes of three late Neandertals (Spy 94a, Mezmaiskaya 2 and El Sidrón 1253). We find that the Denisovan Y chromosomes split around 700 thousand years ago (kya) from a lineage shared by Neandertal and modern human Y chromosomes, which diverged from each other around 370 kya. The phylogenetic relationships of archaic and modern human Y chromosomes therefore differ from population relationships inferred from their autosomal genomes, and mirror the relationships observed on the level of mitochondrial DNA. This provides strong evidence that gene flow from an early lineage related to modern humans resulted in the replacement of both the mitochondrial and Y chromosomal gene pools in late Neandertals. Although unlikely under neutrality, we show that this replacement is plausible if the low effective population size of Neandertals resulted in an increased genetic load in their Y chromosomes and mitochondrial DNA relative to modern humans.

113: Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening
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Posted to bioRxiv 29 Jan 2020

Therapeutic Drugs Targeting 2019-nCoV Main Protease by High-Throughput Screening
1,312 downloads pharmacology and toxicology

Yan Li, Jinyong Zhang, Ning Wang, Haibo Li, Yun Shi, Gang Guo, Kaiyun Liu, Hao Zeng, Quanming Zou

2019 Novel Coronavirus (2019-nCoV) is a virus identified as the cause of the outbreak of pneumonia first detected in Wuhan, China. Investigations on the transmissibility, severity, and other features associated with this virus are ongoing. Currently, there is no vaccine or therapeutic antibody to prevent the infection, and more time is required to develop an effective immune strategy against the pathogen. In contrast, specific inhibitors targeting the key protease involved in replication and proliferation of the virus are the most effective means to alleviate the epidemic. The main protease of SARS-CoV is essential for the life cycle of the virus, which showed 96.1% of similarity with the main proteaseof 2019-nCoV, is considered to be an attractive target for drug development. In this study, we have identified 4 small molecular drugs with high binding capacity with SARS-CoV main protease by high-throughput screening based on the 8,000 clinical drug libraries, all these drugs have been widely used in clinical applications with guaranteed safety, which may serve as promising candidates to treat the infection of 2019-nCoV.

114: Split-TurboID enables contact-dependent proximity labeling in cells
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Posted to bioRxiv 12 Mar 2020

Split-TurboID enables contact-dependent proximity labeling in cells
1,295 downloads cell biology

Kelvin F Cho, Tess C Branon, Sanjana Rajeev, Tanya Svinkina, Namrata D Udeshi, Themis Thoudam, Chulhwan Kwak, Hyun-Woo Rhee, In-Kyu Lee, Steven A. Carr, Alice Y. Ting

Proximity labeling (PL) catalyzed by promiscuous enzymes such as TurboID have enabled the proteomic analysis of subcellular regions difficult or impossible to access by conventional fractionation-based approaches. Yet some cellular regions, such as organelle contact sites, remain out of reach for current PL methods. To address this limitation, we split the enzyme TurboID into two inactive fragments that recombine when driven together by a protein-protein interaction or membrane-membrane apposition. At endoplasmic reticulum (ER)-mitochondria contact sites, reconstituted TurboID catalyzed spatially-restricted biotinylation, enabling the enrichment and identification of >100 endogenous proteins, including many not previously linked to ER-mitochondria contacts. We validated eight novel candidates by biochemical fractionation and overexpression imaging. Overall, split-TurboID is a versatile tool for conditional and spatially-specific proximity labeling in cells.

115: Molecular Dynamics Simulations Indicate the SARS-CoV-2 Mpro Is Not a Viable Target for Small-Molecule Inhibitors Design
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Posted to bioRxiv 02 Mar 2020

Molecular Dynamics Simulations Indicate the SARS-CoV-2 Mpro Is Not a Viable Target for Small-Molecule Inhibitors Design
1,278 downloads molecular biology

Maria Bzowka, Karolina Mitusinska, Agata Raczynska, Aleksandra Samol, Jack A. Tuszynski, Artur Gora

The coronavirus outbreak took place in December 2019 and continues to spread worldwide. In the absence of an effective vaccine, inhibitor repurposing may seem a fruitful attempt. Here, we compared Mpros from SARS-CoV-2 and SARS-CoV. Despite a high level of sequence similarity, the binding sites of analysed proteins show major differences in both shape and size indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, the analysis of the pockets' conformational changes during the simulation time indicates their flexibility, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the SARS-CoV-2 Mpro with respect to mutations of the binding cavity and adjacent flexible loops indicates that the protein's mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.

116: Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections
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Posted to bioRxiv 17 Mar 2020

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections
1,260 downloads microbiology

Huibin Lv, Nicholas C. Wu, Owen Tak-Yin Tsang, Meng Yuan, Ranawaka A. P. M. Perera, Wai Shing Leung, Ray T. Y. So, Jacky Man Chun Chan, Garrick K. Yip, Thomas Shiu Hong Chik, Yiquan Wang, Chris Yau Chung Choi, Yihan Lin, Wilson W. Ng, Jincun Zhao, Leo L. M. Poon, J. S. Malik Peiris, Ian A. Wilson, Chris K. P. Mok

The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

117: The 2019-new Coronavirus epidemic: evidence for virus evolution
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Posted to bioRxiv 24 Jan 2020

The 2019-new Coronavirus epidemic: evidence for virus evolution
1,246 downloads bioinformatics

Domenico Benvenuto, Marta Giovannetti, Alessandra Ciccozzi, Silvia Spoto, Silvia Angeletti, Massimo Ciccozzi

There is concern about a new coronavirus, the 2019-nCoV, as a global public health threat. In this article, we provide a preliminary evolutionary and molecular epidemiological analysis of this new virus. A phylogenetic tree has been built using the 15 available whole genome sequence of 2019-nCoV and 12 whole genome sequences highly similar sequences available in gene bank (5 from SARS, 2 from MERS and 5 from Bat SARS-like Coronavirus). FUBAR analysis shows that the Nucleocapsid and the Spike Glycoprotein has some sites under positive pressure while homology modelling helped to explain some molecular and structural differences between the viruses. The phylogenetic tree showed that 2019.nCoV significantly clustered with Bat SARS-like Coronavirus sequence isolated in 2015, whereas structural analysis revealed mutation in S and nucleocapsid proteins. From these results, 2019nCoV could be considered a coronavirus distinct from SARS virus, probably transmitted from bats or another host where mutations conferred upon it the ability to infect humans.

118: Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach
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Posted to bioRxiv 11 Feb 2020

Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach
1,244 downloads bioinformatics

Miyssa I. Abdelmageed, Abdelrahman H. Abdelmoneim, Mujahed I. Mustafa, Nafisa M. Elfadol, Naseem S. Murshed, Shaza W Shantier, Abdelrafie M. Makhawi

Background New endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a “public-health emergency of international concern” due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach. Method Several techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target. Results Extensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. Conclusion T cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks. * WHO : World Health Organization CoV : Coronaviruses MERS-CoV : Middle East Respiratory Syndrome SARS-CoV : Acute Respiratory Syndrome COVID-19 : novel coronavirus HCoV-HKU1 : Human coronavirus HKU1 HCoV-OC43 : Human coronavirus OC43 HCoV-NL63 : Human coronavirus NL63 HCoV-229E : Human coronavirus 229E ACE2 : angiotensin converting enzyme 2 RBM : receptor-binding motif RBM : receptor-binding domain vs : versus ACT : Artemis Comparison Tool ACC : auto cross covariance MEGA : Molecular Evolutionary Genetics Analysis ANN : Artificial Neural Network IEDB : Immune Epitope Database IC50 : median inhibitory concentrations MHC I : Major Histocompatibility complex class I MHC II : Major Histocompatibility complex class II PDB : Protein database MSA : multiple sequence alignment

119: Machine intelligence design of 2019-nCoV drugs
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Posted to bioRxiv 04 Feb 2020

Machine intelligence design of 2019-nCoV drugs
1,241 downloads bioinformatics

Kaifu Gao, Duc Duy Nguyen, Rui Wang, Guo-Wei Wei

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) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV 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.

120: Machine translation of cortical activity to text with an encoder-decoder framework
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Posted to bioRxiv 22 Jul 2019

Machine translation of cortical activity to text with an encoder-decoder framework
1,240 downloads neuroscience

Joseph G. Makin, David A. Moses, Edward F. Chang

A decade after the first successful attempt to decode speech directly from human brain signals, accuracy and speed remain far below that of natural speech or typing. Here we show how to achieve high accuracy from the electrocorticogram at natural-speech rates, even with few data (on the order of half an hour of spoken speech). Taking a cue from recent advances in machine translation and automatic speech recognition, we train a recurrent neural network to map neural signals directly to word sequences (sentences). In particular, the network first encodes a sentence-length sequence of neural activity into an abstract representation, and then decodes this representation, word by word, into an English sentence. For each participant, training data consist of several spoken repeats of a set of some 30-50 sentences, along with the corresponding neural signals at each of about 250 electrodes distributed over peri-Sylvian speech cortices. Average word error rates across a validation (held-out) sentence set are as low as 7% for some participants, as compared to the previous state of the art of greater than 60%. Finally, we show how to use transfer learning to overcome limitations on data availability: Training certain components of the network under multiple participants' data, while keeping other components (e.g., the first hidden layer) "proprietary," can improve decoding performance--despite very different electrode coverage across participants.

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