Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 94,912 bioRxiv papers from 404,161 authors.

Most downloaded bioRxiv papers, since beginning of last month

93,099 results found. For more information, click each entry to expand.

81: Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
more details view paper

Posted to bioRxiv 15 May 2020

Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
1,655 downloads immunology

Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West, Charles M. Rice, Theodora Hatziioannou, Pamela J Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective. ### Competing Interest Statement In connection with this work The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N are inventors.

82: The tiny Cretaceous stem-bird Oculudentavis revealed as a bizarre lizard
more details view paper

Posted to bioRxiv 10 Aug 2020

The tiny Cretaceous stem-bird Oculudentavis revealed as a bizarre lizard
1,647 downloads paleontology

Arnau Bolet, Edward L. Stanley, Juan D. Daza, J. Salvador Arias, Andrej Čerňanský, Marta Vidal-García, Aaron M. Bauer, Joseph J. Bevitt, Adolf Peretti, Susan E. Evans

Oculudentavis khaungraae was described based on a tiny skull trapped in amber. The slender tapering rostrum with retracted osseous nares, large eyes, and short vaulted braincase led to its identification as the smallest avian dinosaur on record, comparable to the smallest living hummingbirds. Despite its bird-like appearance, Oculudentavis showed several features inconsistent with its original phylogenetic placement. Here we describe a more complete, specimen that demonstrates Oculudentavis is actually a bizarre lizard of uncertain position. The new interpretation and phylogenetic placement highlights a rare case of convergent evolution rarely seen among reptiles. Our results re-affirm the importance of Myanmar amber in yielding unusual taxa from a forest ecosystem rarely represented in the fossil record. ### Competing Interest Statement The authors have declared no competing interest.

83: Complementary roles of dimensionality and population structure in neural computations
more details view paper

Posted to bioRxiv 04 Jul 2020

Complementary roles of dimensionality and population structure in neural computations
1,642 downloads neuroscience

Alexis Dubreuil, Adrian Valente, Manuel Beiran, Francesca Mastrogiuseppe, Srdjan Ostojic

Neural computations are currently investigated using two competing approaches: sorting neurons into functional classes, or examining the low-dimensional dynamics of collective activity. Whether and how these two aspects interact to shape computations is currently unclear. Using a novel approach to extract computational mechanisms from networks trained with machine-learning tools on neuroscience tasks, here we show that the dimensionality of the dynamics and cell-class structure play fundamentally complementary roles. While various tasks can be implemented by increasing the dimensionality in networks consisting of a single global population, flexible input-output mappings instead required networks to be organized into several sub-populations. Our analyses revealed that the subpopulation structure enabled flexible computations through a mechanism based on gain-controlled modulations that flexibly shape the dynamical landscape of collective dynamics. Our results lead to task-specific predictions for the structure of neural selectivity and inactivation experiments. ### Competing Interest Statement The authors have declared no competing interest.

84: Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2
more details view paper

Posted to bioRxiv 12 Apr 2020

Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2
1,642 downloads microbiology

Arinjay Banerjee, Jalees A. Nasir, Patrick Budylowski, Lily Yip, Patryk Aftanas, Natasha Christie, Ayoob Ghalami, Kaushal Baid, Amogelang R. Raphenya, Jeremy A. Hirota, Matthew S Miller, Allison J McGeer, Mario Ostrowski, Robert A. Kozak, Andrew G McArthur, Karen Mossman, Samira Mubareka

SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 107,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two cases of COVID-19 in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we tested a wide range of human immune cells for productive infection with SARS-CoV-2. Here we confirm that human primary peripheral blood mononuclear cells (PBMCs) are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype using in vitro and in vivo infection models. ### Competing Interest Statement The authors have declared no competing interest.

85: Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
more details view paper

Posted to bioRxiv 23 May 2020

Deep immune profiling of COVID-19 patients reveals patient heterogeneity and distinct immunotypes with implications for therapeutic interventions
1,638 downloads immunology

Divij Mathew, Josephine R Giles, Amy E. Baxter, Allison R. Greenplate, Jennifer E Wu, Cécile Alanio, Derek A. Oldridge, Leticia Kuri-Cervantes, M. Betina Pampena, Kurt D’Andrea, Sasikanth Manne, Zeyu Chen, Yinghui Jane Huang, John P Reilly, Ariel R Weisman, Caroline A.G. Ittner, Oliva Kuthuru, Jeanette Dougherty, Kito Nzingha, Nicholas Han, Justin Kim, Ajinkya Pattekar, Eileen C. Goodwin, Elizabeth M Anderson, Madison E. Weirick, Sigrid Gouma, Claudia P Arevalo, Marcus J Bolton, Fang Chen, Simon F. Lacey, Scott E. Hensley, Sokratis Apostolidis, Alexander C Huang, Laura A. Vella, The UPenn COVID Processing Unit, Michael R. Betts, Nuala J. Meyer, E. John Wherry

COVID-19 has become a global pandemic. Immune dysregulation has been implicated, but immune responses remain poorly understood. We analyzed 71 COVID-19 patients compared to recovered and healthy subjects using high dimensional cytometry. Integrated analysis of ~200 immune and >30 clinical features revealed activation of T cell and B cell subsets, but only in some patients. A subgroup of patients had T cell activation characteristic of acute viral infection and plasmablast responses could reach >30% of circulating B cells. However, another subgroup had lymphocyte activation comparable to uninfected subjects. Stable versus dynamic immunological signatures were identified and linked to trajectories of disease severity change. These analyses identified three immunotypes associated with poor clinical trajectories versus improving health. These immunotypes may have implications for therapeutics and vaccines. ### Competing Interest Statement The authors have declared no competing interest.

86: Spatial tissue profiling by imaging-free molecular tomography
more details view paper

Posted to bioRxiv 04 Aug 2020

Spatial tissue profiling by imaging-free molecular tomography
1,595 downloads genomics

Halima Hannah Schede, Christian G. Schneider, Johanna Stergiadou, Lars E. Borm, Anurag Ranjak, Tracy M. Yamawaki, Fabrice P.A. David, Peter Lönnerberg, Gilles Laurent, Maria Antonietta Tosches, Simone Codeluppi, Gioele La Manno

Genomics techniques are currently being adapted to provide spatially resolved omics profiling. However, the adaptation of each new method typically requires the setup of specific detection strategies or specialized instrumentation. A generic approach to spatially resolve different types of high throughput data is missing. Here, we describe an imaging-free framework to localize high throughput readouts within a tissue by combining compressive sampling and image reconstruction. We implemented this framework to transform a low-input RNA sequencing protocol into an imaging-free spatial transcriptomics technique (STRP-seq) and validated this method with a transcriptome profiling of the murine brain. To verify the broad applicability of STRP-seq, we applied the technique on the brain of the Australian bearded dragon Pogona vitticeps. Our results reveal the molecular anatomy of the telencephalon of this lizard, providing evidence for a marked regionalization of the reptilian pallium and subpallium. Overall, the proposed framework constitutes a new approach that allows upgrading in a generic fashion conventional genomic assays to spatially resolved techniques. ### Competing Interest Statement The authors have declared no competing interest.

87: Neuropilin-1 is a host factor for SARS-CoV-2 infection
more details view paper

Posted to bioRxiv 05 Jun 2020

Neuropilin-1 is a host factor for SARS-CoV-2 infection
1,589 downloads cell biology

James L Daly, Boris Simonetti, Carlos Antón-Plágaro, Maia Kavanagh Williamson, Deborah K. Shoemark, Lorena Simón-Gracia, Katja Klein, Michael Bauer, Reka Hollandi, Urs F. Greber, Peter Horvath, Richard B. Sessions, Ari Helenius, Julian A Hiscox, Tambet Teesalu, David A. Matthews, Andrew D. Davidson, Peter J. Cullen, Yohei Yamauchi

SARS-CoV-2 is the causative agent of COVID-19, a coronavirus disease that has infected more than 6.6 million people and caused over 390,000 deaths worldwide. The Spike (S) protein of the virus forms projections on the virion surface responsible for host cell attachment and penetration. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2. For SARS-CoV-2 the cleavage is catalysed by furin, a host cell protease, which cleaves the S protein precursor at a specific sequence motif that generates a polybasic Arg-Arg-Ala-Arg (RRAR) C-terminal sequence on S1. This sequence motif conforms to the C-end rule (CendR), which means that the C-terminal sequence may allow the protein to associate with cell surface neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors. Here we demonstrate using immunoprecipitation, site-specific mutagenesis, structural modelling, and antibody blockade that, in addition to engaging the known receptor ACE2, S1 can bind to NRP1 through the canonical CendR mechanism. This interaction enhances infection by SARS-CoV-2 in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection, and provides a therapeutic target for COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

88: SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence?
more details view paper

Posted to bioRxiv 02 May 2020

SARS-CoV-2 is well adapted for humans. What does this mean for re-emergence?
1,582 downloads evolutionary biology

Shing Hei Zhan, Benjamin E. Deverman, Yujia Alina Chan

In a side-by-side comparison of evolutionary dynamics between the 2019/2020 SARS-CoV-2 and the 2003 SARS-CoV, we were surprised to find that SARS-CoV-2 resembles SARS-CoV in the late phase of the 2003 epidemic after SARS-CoV had developed several advantageous adaptations for human transmission. Our observations suggest that by the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV. However, no precursors or parallel branches of evolution stemming from a less human-adapted SARS-CoV-2-like virus have been detected. The sudden appearance of a highly infectious SARS-CoV-2 presents a major cause for concern that should motivate stronger international efforts to identify the source and prevent near future re-emergence. Any existing pools of SARS-CoV-2 progenitors would be particularly dangerous if similarly well adapted for human transmission. To look for clues regarding intermediate hosts, we analyze recent key findings relating to how SARS-CoV-2 could have evolved and adapted for human transmission, and examine the environmental samples from the Wuhan Huanan seafood market. Importantly, the market samples are genetically identical to human SARS-CoV-2 isolates and were therefore most likely from human sources. We conclude by describing and advocating for measured and effective approaches implemented in the 2002-2004 SARS outbreaks to identify lingering population(s) of progenitor virus. ### Competing Interest Statement Shing Hei Zhan is a Co-founder and lead bioinformatics scientist at Fusion Genomics Corporation, which develops molecular diagnostic assays for infectious diseases.

89: The emergence of SARS-CoV-2 in Europe and the US
more details view paper

Posted to bioRxiv 23 May 2020

The emergence of SARS-CoV-2 in Europe and the US
1,566 downloads genetics

Michael Worobey, Jonathan Pekar, Brendan B Larsen, Martha I. Nelson, Verity Hill, Jeffrey B. Joy, Andrew Rambaut, Marc A. Suchard, Joel O. Wertheim, Philippe Lemey

Accurate understanding of the global spread of emerging viruses is critically important for public health response and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and the United States (US). Our results refute prior findings erroneously linking cases in January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward transmission of those early cases in Germany and Washington State. Other, later introductions of the virus from China to both Italy and Washington State founded the earliest sustained European and US transmission networks. Our analyses reveal an extended period of missed opportunity when intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe. ### Competing Interest Statement JOW has received funding from Gilead Sciences, LLC (completed) and the CDC (ongoing) via grants and contracts to his institution unrelated to this research. MAS receives funding from Janssen Research & Development, IQVIA and Private Health Management via contracts unrelated to this research.

90: Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes
more details view paper

Posted to bioRxiv 05 May 2020

Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes
1,556 downloads genomics

Chandrika Bhattacharyya, Chitrarpita Das, Arnab Ghosh, Animesh K Singh, Souvik Mukherjee, Partha P. Majumder, Analabha Basu, Nidhan K. Biswas

COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare. ### Competing Interest Statement The authors have declared no competing interest.

91: Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions
more details view paper

Posted to bioRxiv 27 Jun 2020

Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions
1,554 downloads microbiology

Zunlong Ke, Joaquin Oton, Kun Qu, Mirko Cortese, Vojtech Zila, Lesley McKeane, Takanori Nakane, Jasenko Zivanov, Christopher J. Neufeldt, John M Lu, Julia Peukes, Xiaoli Xiong, Hans-Georg Kräusslich, Sjors H.W. Scheres, Ralf Bartenschlager, John A.G. Briggs

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates the exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy. The structure and distribution of S on the virion surface, however, has not been characterised. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distributions of S trimers in situ on the virion surface. These results provide a basis for understanding the conformations of S present on the virion, and for studying their interactions with neutralizing antibodies. ### Competing Interest Statement The authors have declared no competing interest.

92: Single-particle cryo-EM at atomic resolution
more details view paper

Posted to bioRxiv 22 May 2020

Single-particle cryo-EM at atomic resolution
1,550 downloads biophysics

Takanori Nakane, Abhay Kotecha, Andrija Sente, Greg McMullan, Simonas Masiulis, Patricia M.G.E. Brown, Ioana T. Grigoras, Lina Malinauskaite, Tomas Malinauskas, Jonas Miehling, Lingbo Yu, Dimple Karia, Evgeniya V. Pechnikova, Erwin de Jong, Jeroen Keizer, Maarten Bischoff, Jamie McCormack, Peter Tiemeijer, Steven W Hardwick, Dimitri Y Chirgadze, Garib Murshudov, A. Radu Aricescu, Sjors H.W. Scheres

The three-dimensional positions of atoms in protein molecules define their structure and provide mechanistic insights into the roles they perform in complex biological processes. The more precisely atomic coordinates are determined, the more chemical information can be derived and the more knowledge about protein function may be inferred. With breakthroughs in electron detection and image processing technology, electron cryo-microscopy (cryo-EM) single-particle analysis has yielded protein structures with increasing levels of detail in recent years. However, obtaining cryo-EM reconstructions with sufficient resolution to visualise individual atoms in proteins has thus far been elusive. Here, we show that using a new electron source, energy filter and camera, we obtained a 1.7 Å resolution cryo-EM reconstruction for a prototypical human membrane protein, the β3 GABAA receptor homopentamer. Such maps allow a detailed understanding of small molecule coordination, visualisation of solvent molecules and alternative conformations for multiple amino acids, as well as unambiguous building of ordered acidic side chains and glycans. Applied to mouse apo-ferritin, our strategy led to a 1.2 Å resolution reconstruction that, for the first time, offers a genuine atomic resolution view of a protein molecule using single particle cryo-EM. Moreover, the scattering potential from many hydrogen atoms can be visualised in difference maps, allowing a direct analysis of hydrogen bonding networks. Combination of the technological advances described here with further approaches to accelerate data acquisition and improve sample quality provide a route towards routine application of cryo-EM in high-throughput screening of small molecule modulators and structure-based drug discovery. ### Competing Interest Statement A.K., S.M., L.Y., D.K., E.V.P., E.d.J., J.K., M.B., J.M., and P.T are employees of Thermo Fisher Scientific.

93: Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2
more details view paper

Posted to bioRxiv 26 Jan 2020

Single-cell RNA expression profiling of ACE2, the receptor of SARS-CoV-2
1,533 downloads bioinformatics

Yu Zhao, Zixian Zhao, Yujia Wang, Yueqing Zhou, Yu Ma, Wei Zuo

A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development. ### Competing Interest Statement The authors have declared no competing interest.

94: De novo design of picomolar SARS-CoV-2 miniprotein inhibitors
more details view paper

Posted to bioRxiv 03 Aug 2020

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors
1,522 downloads synthetic biology

Longxing Cao, Inna Goreshnik, Brian Coventry, James Brett Case, Lauren Miller, Lisa Kozodoy, Rita E. Chen, Lauren Carter, Lexi Walls, Young-Jun Park, Lance Stewart, Michael Diamond, David Veesler, David Baker

We used two approaches to design proteins with shape and chemical complementarity to the receptor binding domain (RBD) of SARS-CoV-2 Spike protein near the binding site for the human ACE2 receptor. Scaffolds were built around an ACE2 helix that interacts with the RBD, or de novo designed scaffolds were docked against the RBD to identify new binding modes. In both cases, designed sequences were optimized first in silico and then experimentally for target binding, folding and stability. Nine designs bound the RBD with affinities ranging from 100pM to 10nM, and blocked bona fide SARS-CoV-2 infection of Vero E6 cells with IC50 values ranging from 35 pM to 35 nM; the most potent of these - 56 and 64 residue hyperstable proteins made using the second approach - are roughly six times more potent on a per mass basis (IC50 ~ 0.23 ng/ml) than the best monoclonal antibodies reported thus far. Cryo-electron microscopy structures of the SARS-CoV-2 spike ectodomain trimer in complex with the two most potent minibinders show that the structures of the designs and their binding interactions with the RBD are nearly identical to the computational models, and that all three RBDs in a single Spike protein can be engaged simultaneously. These hyperstable minibinders provide promising starting points for new SARS-CoV-2 therapeutics, and illustrate the power of computational protein design for rapidly generating potential therapeutic candidates against pandemic threats. ### Competing Interest Statement The authors have declared no competing interest.

95: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD
more details view paper

Posted to bioRxiv 20 Mar 2020

Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD
1,513 downloads bioengineering

G. Zhang, S. Pomplun, A. R. Loftis, X. Tan, A. Loas, B. L. Pentelute

Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 7 million confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved cryo-EM structure of ACE2 in complex with SARS-CoV-2-RBD, we observed that the ACE2 peptidase domain (PD) α1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD α1 helix (SBP1) composed entirely of proteinogenic amino acids. Chemical synthesis of SBP1 was complete in 1.5 hours, and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry (BLI) revealed that SBP1 associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein obtained from Sino Biological. Association of SBP1 was not observed to an appreciable extent to HEK cell-expressed SARS-CoV-2-RBD proteins and insect-derived variants acquired from other vendors. Moreover, competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD. Further investigations are ongoing to gain insight into the molecular and structural determinants of the variable binding behavior to different SARS-CoV-2-RBD protein variants. ### Competing Interest Statement Bradley L. Pentelute is a co-founder of Resolute Bio and Amide Technologies.

96: A single-cell method to map higher-order 3D genome organization in thousands of individual cells reveals structural heterogeneity in mouse ES cells
more details view paper

Posted to bioRxiv 12 Aug 2020

A single-cell method to map higher-order 3D genome organization in thousands of individual cells reveals structural heterogeneity in mouse ES cells
1,497 downloads molecular biology

Mary V. Arrastia, Joanna W. Jachowicz, Noah Ollikainen, Matthew S. Curtis, Charlotte Lai, Sofia A. Quinodoz, David A. Selck, Mitchell Guttman, Rustem F. Ismagilov

In eukaryotes, the nucleus is organized into a three dimensional structure consisting of both local interactions such as those between enhancers and promoters, and long-range higher-order structures such as nuclear bodies. This organization is central to many aspects of nuclear function, including DNA replication, transcription, and cell cycle progression. Nuclear structure intrinsically occurs within single cells; however, measuring such a broad spectrum of 3D DNA interactions on a genome-wide scale and at the single cell level has been a great challenge. To address this, we developed single-cell split-pool recognition of interactions by tag extension (scSPRITE), a new method that enables measurements of genome-wide maps of 3D DNA structure in thousands of individual nuclei. scSPRITE maximizes the number of DNA contacts detected per cell enabling high-resolution genome structure maps within each cells and is easy-to-use and cost-effective. scSPRITE accurately detects chromosome territories, active and inactive compartments, topologically associating domains (TADs), and higher-order structures within single cells. In addition, scSPRITE measures cell-to-cell heterogeneity in genome structure at different levels of resolution and shows that TADs are dynamic units of genome organization that can vary between different cells within a population. scSPRITE will improve our understanding of nuclear architecture and its relationship to nuclear function within an individual nucleus from complex cell types and tissues containing a diverse population of cells. ### Competing Interest Statement This paper is the subject of a patent application filed by Caltech. R.F.I. has a financial interest in Talis Biomedical Corp.

97: An index of the quality of evidence in meta-analysis of randomized controlled trials
more details view paper

Posted to bioRxiv 13 Jan 2017

An index of the quality of evidence in meta-analysis of randomized controlled trials
1,495 downloads scientific communication and education

Devon D. Brewer

The quality of evidence in meta-analysis of randomized controlled trials is the degree to which the estimated effect represents the "truth." Current approaches to assessing the quality of evidence focus on trial design and methods. I describe a new quality of evidence index composed of four sub-indexes that measure pre-registration, independent replication, data availability, and trial design and methods, respectively. This index is systematic, objective, and quantitative. I illustrate the index with an empirical example and provide a spreadsheet for easy calculation.

98: The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I
more details view paper

Posted to bioRxiv 24 May 2020

The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I
1,468 downloads microbiology

Yiwen Zhang, Junsong Zhang, Yingshi Chen, Baohong Luo, Yaochang Yuan, Feng Huang, Tao Yang, Fei Yu, Jun Liu, Bingfen Liu, Zheng Song, Jingliang Chen, Ting Pan, Xu Zhang, Yuzhuang Li, Rong Li, Wenjing Huang, Fei Xiao, Hui Zhang

SARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo. ### Competing Interest Statement The authors have declared no competing interest.

99: Multi-Platform Assessment of DNA Sequencing Performance using Human and Bacterial Reference Genomes in the ABRF Next-Generation Sequencing Study
more details view paper

Posted to bioRxiv 24 Jul 2020

Multi-Platform Assessment of DNA Sequencing Performance using Human and Bacterial Reference Genomes in the ABRF Next-Generation Sequencing Study
1,466 downloads genomics

Jonathan Foox, Scott W Tighe, Charles M Nicolet, Justin M Zook, Marta Byrska-Bishop, Wayne E. Clarke, Michael M Khayat, Medhat Mahmoud, Phoebe K Laaguiby, Zachary T Herbert, Derek Warner, George S Grills, Jin Jen, Shawn Levy, Jenny Xiang, Alicia Alonso, Gary P Schroth, Fritz J. Sedlazeck, Giuseppe Narzisi, William Farmerie, Don A Baldwin, Christopher E. Mason

Massively parallel DNA sequencing is a critical tool for genomics research and clinical diagnostics. Here, we describe the Association of Biomolecular Resource Facilities (ABRF) Next-Generation Sequencing Phase II Study to measure quality and reproducibility of DNA sequencing. Replicates of human and bacterial reference DNA samples were generated across multiple sequencing platforms, including well-established technologies such as Illumina, ThermoFisher Ion Torrent, and Pacific Biosciences, as well as emerging technologies such as BGI, Genapsys, and Oxford Nanopore. A total of 202 datasets were generated to investigate the performance of a total of 16 sequencing platforms, including mappability of reads, coverage and error rates in difficult genomic regions, and detection of small-scale polymorphisms and large-scale structural variants. This study provides a comprehensive baseline resource for continual benchmarking as chemistries, methods, and platforms evolve for DNA sequencing. ### Competing Interest Statement G.P.S is employed by Illumina Inc. All other authors declare no competing financial interests.

100: Open Science Saves Lives: Lessons from the COVID-19 Pandemic
more details view paper

Posted to bioRxiv 14 Aug 2020

Open Science Saves Lives: Lessons from the COVID-19 Pandemic
1,445 downloads scientific communication and education

Lonni Besançon, Nathan Peiffer-Smadja, Corentin Segalas, Haiting Jiang, Paola Masuzzo, Cooper Smout, Maxime Deforet, Clémence Leyrat

In the last decade Open Science principles, such as Open Access, study preregistration, use of preprints, making available data and code, and open peer review, have been successfully advocated for and are being slowly adopted in many different research communities. In response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of some of these Open Science practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner. In this article, we express concerns about the violation of some of the Open Science principles and its potential impact on the quality of research output. We provide evidence of the misuses of these principles at different stages of the scientific process. We call for a wider adoption of Open Science practices in the hope that this work will encourage a broader endorsement of Open Science principles and serve as a reminder that science should always be a rigorous process, reliable and transparent, especially in the context of a pandemic where research findings are being translated into practice even more rapidly. We provide all data and scripts at https://osf.io/renxy/. ### Competing Interest Statement The authors have declared no competing interest.

Previous page 1 2 3 4 5 6 7 8 9 . . . 4655 Next page

PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News