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.
58,313 downloads immunology
Takuya Sekine, André Perez-Potti, Olga Rivera-Ballesteros, Kristoffer Strålin, Jean-Baptiste Gorin, Annika Olsson, Sian Llewellyn-Lacey, Habiba Kamal, Gordana Bogdanovic, Sandra Muschiol, David J. Wullimann, Tobias Kammann, Johanna Emgård, Tiphaine Parrot, Elin Folkesson, Olav Rooyackers, Lars I Eriksson, Anders Sönnerborg, Tobias Allander, Jan Albert, Morten Nielsen, Jonas Klingström, Sara Gredmark-Russ, Niklas K Björkström, Johan K. Sandberg, David A. Price, Hans-Gustaf Ljunggren, Soo Aleman, Marcus Buggert, Karolinska COVID-19 Study Group
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals. ### Competing Interest Statement The authors have declared no competing interest.
27,156 downloads genomics
A recent genetic association study (Ellinghaus et al. 2020) identified a gene cluster on chromosome 3 as a risk locus for respiratory failure in SARS-CoV-2. Recent data comprising 3,199 hospitalized COVID-19 patients and controls reproduce this and find that it is the major genetic risk factor for severe SARS-CoV-2 infection and hospitalization (COVID-19 Host Genetics Initiative). Here, we show that the risk is conferred by a genomic segment of ~50 kb that is inherited from Neandertals and occurs at a frequency of ~30% in south Asia and ~8% in Europe. ### Competing Interest Statement The authors have declared no competing interest.
14,987 downloads evolutionary biology
This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results. If you have any questions, please contact the corresponding author.
14,166 downloads neuroscience
Brain-machine interfaces (BMIs) hold promise for the restoration of sensory and motor function and the treatment of neurological disorders, but clinical BMIs have not yet been widely adopted, in part because modest channel counts have limited their potential. In this white paper, we describe Neuralink’s first steps toward a scalable high-bandwidth BMI system. We have built arrays of small and flexible electrode “threads”, with as many as 3,072 electrodes per array distributed across 96 threads. We have also built a neurosurgical robot capable of inserting six threads (192 electrodes) per minute. Each thread can be individually inserted into the brain with micron precision for avoidance of surface vasculature and targeting specific brain regions. The electrode array is packaged into a small implantable device that contains custom chips for low-power on-board amplification and digitization: the package for 3,072 channels occupies less than (23 × 18.5 × 2) mm3. A single USB-C cable provides full-bandwidth data streaming from the device, recording from all channels simultaneously. This system has achieved a spiking yield of up to 70% in chronically implanted electrodes. Neuralink’s approach to BMI has unprecedented packaging density and scalability in a clinically relevant package.
13,134 downloads evolutionary biology
B Korber, WM Fischer, S Gnanakaran, H Yoon, J Theiler, W Abfalterer, B Foley, EE Giorgi, T Bhattacharya, MD Parker, DG Partridge, CM Evans, TM Freeman, TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group, CC LaBranche, DC Montefiori
We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified fourteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; after beginning to spread in Europe in early February, when introduced to new regions it repeatedly and rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions. ### Competing Interest Statement The authors have declared no competing interest.
11,139 downloads microbiology
Neeltje van Doremalen, Teresa Lambe, Alexandra Spencer, Sandra Belij-Rammerstorfer, Jyothi N. Purushotham, Julia R. Port, Victoria Avanzato, Trenton Bushmaker, Amy Flaxman, Marta Ulaszewska, Friederike Feldmann, Elizabeth R. Allen, Hannah Sharpe, Jonathan Schulz, Myndi Holbrook, Atsushi Okumura, Kimberly Meade-White, Lizzette Pérez-Pérez, Cameron Bissett, Ciaran Gilbride, Brandi N. Williamson, Rebecca Rosenke, Dan Long, Alka Ishwarbhai, Reshma Kailath, Louisa Rose, Susan Morris, Claire Powers, Jamie Lovaglio, Patrick W. Hanley, Dana Scott, Greg Saturday, Emmie de Wit, Sarah C. Gilbert, Vincent J. Munster
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials. ### Competing Interest Statement SCG is a board member of Vaccitech and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering a SARS-CoV-2 (nCoV-19) vaccine. Teresa Lambe is named as an inventor on a patent application covering a SARS-CoV-2 (nCoV-19) vaccine. The remaining authors declare no competing interests.
10,723 downloads microbiology
SARS coronavirus 2 (SARS-CoV-2) isolates encoding a D614G mutation in the viral spike (S) protein predominate over time in locales where it is found, implying that this change enhances viral transmission. We therefore compared the functional properties of the S proteins with aspartic acid (SD614) and glycine (SG614) at residue 614. We observed that retroviruses pseudotyped with SG614 infected ACE2-expressing cells markedly more efficiently than those with SD614. This greater infectivity was correlated with less S1 shedding and greater incorporation of the S protein into the pseudovirion. Similar results were obtained using the virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, SG614 did not bind ACE2 more efficiently than SD614, and the pseudoviruses containing these S proteins were neutralized with comparable efficiencies by convalescent plasma. These results show SG614 is more stable than SD614, consistent with epidemiological data suggesting that viruses with SG614 transmit more efficiently. ### Competing Interest Statement The authors have declared no competing interest.
10,009 downloads biochemistry
Michael Schoof, Bryan Faust, Reuben A. Saunders, Smriti Sangwan, Veronica Rezelj, Nick Hoppe, Morgane Boone, Christian B. Billesbølle, Cristina Puchades, Caleigh M. Azumaya, Huong T. Kratochvil, Marcell Zimanyi, Ishan Deshpande, Jiahao Liang, Sasha Dickinson, Henry C. Nguyen, Cynthia M Chio, Gregory E Merz, Michael C Thompson, Devan Diwanji, Kaitlin Schaefer, Aditya A. Anand, Niv Dobzinski, Beth Shoshana Zha, Camille R. Simoneau, Kristoffer Leon, Kris M. White, Un Seng Chio, Meghna Gupta, Mingliang Jin, Fei Li, Yanxin Liu, Kaihua Zhang, David Bulkley, Ming Sun, Amber M. Smith, Alexandrea N. Rizo, Frank R. Moss, Axel F. Brilot, Sergei Pourmal, Raphael Trenker, Thomas Pospiech, Sayan Gupta, Benjamin Barsi-Rhyne, Vladislav Belyy, Andrew W. Barile-Hill, Silke Nock, Yuwei Liu, Nevan J. Krogan, Corie Y. Ralston, Danielle L. Swaney, Adolfo García-Sastre, Melanie Ott, Marco Vignuzzi, QCRG Structural Biology Consortium, Peter Walter, Aashish Manglik
Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century. ### Competing Interest Statement M.Schoof, B.Faust, R.Saunders, N.Hoppe, P.Walter, and A.Manglik are inventors on a provisional patent describing anti-Spike nanobodies described in this manuscript.
7,574 downloads microbiology
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C. C. Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D Hillyer, Marina Caskey, Davide F. Robbiani, Charles M. Rice, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes. ### Competing Interest Statement Patent applications submitted by Rockefeller University are pending for anti SARS-CoV-2 antibodies (MCN, DR, inventors) and VSV/SARS-CoV-2 chimeric virus (PDB, TH, FS and YW, inventors)
6,945 downloads immunology
Kevin W Ng, Nikhil Faulkner, Georgina H. Cornish, Annachiara Rosa, Ruth Harvey, Saira Hussain, Rachel Ulferts, Christopher Earl, Antoni Wrobel, Donald Benton, Chloe Roustan, William Bolland, Rachael Thompson, Ana Agua-Doce, Philip Hobson, Judith Heaney, Hannah Rickman, Stavroula Paraskevopoulou, Catherine F Houlihan, Kirsty Thomson, Emilie Sanchez, David Brealey, Gee Yen Shin, Moira J Spyer, Dhira Joshi, Nicola O’Reilly, Philip A Walker, Svend Kjaer, Andrew Riddell, Catherine Moore, Bethany R Jebson, Meredyth G.Ll. Wilkinson, Lucy R Marshall, Elizabeth C Rosser, Anna Radziszewska, Hannah Peckham, Coziana Ciurtin, Lucy R Wedderburn, Rupert Beale, Charles Swanton, Sonia Gandhi, Brigitta Stockinger, John P. McCauley, Steve Gamblin, Laura E McCoy, Peter Cherepanov, Eleni Nastouli, George Kassiotis
Several related human coronaviruses (HCoVs) are endemic in the human population, causing mild respiratory infections. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiologic agent of Coronavirus disease 2019 (COVID-19), is a recent zoonotic infection that has quickly reached pandemic proportions. Zoonotic introduction of novel coronaviruses is thought to occur in the absence of pre-existing immunity in the target human population. Using diverse assays for detection of antibodies reactive with the SARS-CoV-2 spike (S) glycoprotein, we demonstrate the presence of pre-existing humoral immunity in uninfected and unexposed humans to the new coronavirus. SARS-CoV-2 S-reactive antibodies were readily detectable by a sensitive flow cytometry- based method in SARS-CoV-2-uninfected individuals and were particularly prevalent in children and adolescents. These were predominantly of the IgG class and targeted the S2 subunit. In contrast, SARS-CoV-2 infection induced higher titres of SARS-CoV-2 S-reactive IgG antibodies, targeting both the S1 and S2 subunits, as well as concomitant IgM and IgA antibodies, lasting throughout the observation period of 6 weeks since symptoms onset. SARS-CoV-2-uninfected donor sera also variably reacted with SARS-CoV-2 S and nucleoprotein (N), but not with the S1 subunit or the receptor binding domain (RBD) of S on standard enzyme immunoassays. Notably, SARS-CoV-2- uninfected donor sera exhibited specific neutralising activity against SARS-CoV-2 and SARS-CoV-2 S pseudotypes, according to levels of SARS-CoV-2 S-binding IgG and with efficiencies comparable to those of COVID-19 patient sera. Distinguishing pre-existing and de novo antibody responses to SARS- CoV-2 will be critical for our understanding of susceptibility to and the natural course of SARS-CoV-2 infection. ### Competing Interest Statement The authors have declared no competing interest.
6,730 downloads microbiology
Andreas Herrmann, Junki Maruyama, Chanyu Yue, Christoph Lahtz, Heyue Zhou, Lisa Kerwin, Whenzong Guo, Yanliang Zhang, William Soo Hoo, Soonpin Yei, Sunkuk Kwon, Yanwen Fu, Sachi Johnson, Arthur Ledesma, Yiran Zhou, Yingcong Zhuang, Elena Yei, Tomasz Adamus, Slobodan Praessler, Henry Ji
Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcgammaR+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcgammaR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcgammaR+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations. ### Competing Interest Statement HJ, YZ, Hui Xie, and WG are listed inventors on U.S. Provisional Application Serial No. 62/993,527 Filed March 23, 2020 entitled "FC-CORONAVIRUS ANTIGEN FUSION PROTEINS, AND NUCLEIC ACIDS, VECTORS, COMPOSITIONS AND METHODS OF USE THEREOF".
6,183 downloads microbiology
Alina Baum, Richard Copin, Dharani Ajithdoss, Anbo Zhou, Kathryn Lanza, Nicole Negron, Min Ni, Yi Wei, Gurinder S. Atwal, Adelekan Oyejide, Yenny Goez-Gazi, John Dutton, Elizabeth Clemmons, Hilary M Staples, Carmen Bartley, Benjamin Klaffke, Kendra Alfson, Michal Gazi, Olga Gonzales, Edward Dick, Ricardo Carrion, Laurent Pessaint, Maciel Porto, Anthony Cook, Renita Brown, Vaneesha Ali, Jack Greenhouse, Tammy Taylor, Hanne Andersen, Mark G Lewis, Neil Stahl, Andrew J Murphy, George D Yancopoulos, Christos A. Kyratsous
An urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail. ### Competing Interest Statement Regeneron authors own options and/or stock of the company. This work has been described in one or more pending provisional patent applications. N.S, A.J.M., G.D.Y. and C.A.K. are officers of Regeneron.
5,943 downloads microbiology
Jing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, James Lague, Alyse D Portnoff, James Norton, Mimi Guebre-Xabier, Bin Zhou, Kelsey Jacobson, Sonia Maciejewski, Rafia Khatoon, Malgorzata Wisniewska, Will Moffitt, Stefanie Kluepfel-Stahl, Betty Ekechukwu, James Papin, Sarathi Boddapati, C. Jason Wong, Pedro A. Piedra, Matthew B. Frieman, Michael J Massare, Louis Fries, Karin Lövgren Bengtsson, Linda Stertman, Larry Ellingsworth, Gregory Glenn, Gale Smith
The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4 and CD8 T cells, CD4 T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M ([NCT04368988]). ### Competing Interest Statement GS, GG, JHT, NP, RH, HZ, MGX, ADP, MJM, MBF and LE contributed to conceptualization of experiments, generation of data and analysis, and interpretation of the results. JHT, RH, NP, SW, HH, JL, JN, BZ, KJ, SM, RK, MW, WM, SKS, BE, SB, CJW, HZ performed experiments. ADP, MGX, JP coordinated projects. MBF, ADP, MJM, LF, PAP, KLB, LS, GG, GS, LE contributed to drafting and making critical revisions with the help of others. : /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04368988&atom=%2Fbiorxiv%2Fearly%2F2020%2F06%2F30%2F2020.06.29.178509.atom
5,848 downloads immunology
Willianne Hoepel, Hung-Jen Chen, Sona Allahverdiyeva, Xue Manz, Jurjan Aman, Amsterdam UMC COVID-19 Biobank, Peter Bonta, Philip Brouwer, Steven de Taeye, Tom Caniels, Karlijn van der Straten, Korneliusz Golebski, Guillermo Griffith, René Jonkers, Mads Larsen, Federica Linty, Annette Neele, Jan Nouta, Frank van Baarle, Cornelis van Drunen, Alexander Vlaar, Godelieve de Bree, Rogier Sanders, Lisa Willemsen, Manfred Wuhrer, Harm Jan Bogaard, Marit van Gils, Gestur Vidarsson, Menno de Winther, Jeroen den Dunnen
For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk. ### Competing Interest Statement The authors have declared no competing interest.
5,756 downloads microbiology
The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs. ### Competing Interest Statement The authors have declared no competing interest.
5,736 downloads immunology
Chintana Chirathaworn, Manit Sripramote, Piti Chalongviriyalert, Supunee Jirajariyavej, Phatharaporn Kiatpanabhikul, Jatuporn Saiyarin, Chulikorn Soudon, Orawan Thienfaidee, Thitisan Palakawong Na Ayuthaya, Chantapat Brukesawan, Dootchai Chaiwanichsiri, Duangnapa Intharasongkroh, Nasamon Wanlapakorn, Jira Chansaenroj, Jiratchaya Puenpa, Ritthideach Yorsaeng, Arunee Thitithanyanont, Rungrueng Kitphati, Anek Mungaomklang, Pijaya Nagavajara, Yong Poovorawan
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 emerged in December 2019 and has spread globally. Although Thailand has been effective at controlling the spread of COVID-19, disease surveillance and information on antibody responses in infected cases and close contacts are needed because there is still no specific treatment or vaccine available. We investigated 217 recovered COVID-19 cases to monitor their viral RNA shedding and production of antibodies against SARS-CoV-2. The presence of antibodies in blood samples from 308 close contacts of COVID-19 cases was also determined. Viral RNA was still detectable in 6.6 % of recovered COVID-19 cases. The most prolonged duration of viral RNA shedding detected in this study was 105 days. IgM, IgG, and IgA antibodies against SARS-CoV-2 were detected in 13.82, 88.48, and 83.41 % of the recovered cases 4–12 weeks after disease onset, respectively. Although the patients had recovered from their illness, the levels of antibodies detected showed association with their symptoms during their stay in hospital. Fifteen of the 308 contacts (4.87 %) of COVID-19 cases tested positive for IgG antibodies. The presence of antibodies against SARS-CoV-2 suggested that there was viral exposure among close contacts. Viral clearance and the pattern of antibody responses in infected individuals are both crucial for effectively combatting SARS-CoV-2. Our study provides additional information on the natural history of this newly emerging disease related to both natural host defenses and a strategy for vaccine development.
5,216 downloads systems biology
David E Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, Jeffrey Z. Guo, Danielle L. Swaney, Tia A Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Wenqi Shen, Ying Shi, Ziyang Zhang, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Christopher J.P. Mathy, Tina Perica, Kala B. Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Rakesh Ramachandran, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Stephanie A. Wankowicz, Markus Bohn, Phillip P. Sharp, Raphael Trenker, Janet M. Young, Devin A. Cavero, Joseph Hiatt, Theodore L. Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Ferdinand Roesch, Thomas Vallet, Björn Meyer, Kris M. White, Lisa Miorin, Oren S. Rosenberg, Kliment A Verba, David A. Agard, Melanie Ott, Michael Emerman, Davide Ruggero, Adolfo García-Sastre, Natalia Jura, Mark von Zastrow, Jack Taunton, Alan Ashworth, Olivier Schwartz, Marco Vignuzzi, Christophe d’Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica Galonić Fujimori, Trey Ideker, Charles S. Craik, Jennifer A. Doudna, James S Fraser, John D. Gross, Andrej Sali, Tanja Kortemme, Pedro Beltrao, Kevan Shokat, Brian K. Shoichet, Nevan J. Krogan
An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption,. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains. * HC-PPIs : High confidence protein-protein interactions PPIs : protein-protein interaction AP-MS : affinity purification-mass spectrometry COVID-19 : Coronavirus Disease-2019 ACE2 : angiotensin converting enzyme 2 Orf : open reading frame Nsp3 : papain-like protease Nsp5 : main protease Nsp : nonstructural protein TPM : transcripts per million : #ref-1 : #ref-2
4,845 downloads immunology
Nina Le Bert, Anthony T Tan, Kamini Kunasegaran, Christine Y. L. Tham, Morteza Hafezi, Adeline Chia, Melissa Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, Antonio Bertoletti
Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic. ### Competing Interest Statement A.B. is a cofounder of Lion TCR, a biotech company developing T cell receptors for treatment of virus-related diseases and cancers. None of the other authors has any competing interest related to the study.
4,769 downloads microbiology
Alexander E. Gorbalenya, Susan C. Baker, Ralph S. Baric, Raoul J. de Groot, Christian Drosten, Anastasia A. Gulyaeva, Bart L. Haagmans, Chris Lauber, Andrey M Leontovich, Benjamin W Neuman, Dmitry Penzar, Stanley Perlman, Leo L.M. Poon, Dmitry Samborskiy, Igor A. Sidorov, Isabel Sola, John Ziebuhr
The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
4,499 downloads immunology
Kizzmekia S. Corbett, Darin Edwards, Sarah R. Leist, Olubukola M. Abiona, Seyhan Boyoglu-Barnum, Rebecca A Gillespie, Sunny Himansu, Alexandra Schäfer, Cynthia T. Ziwawo, Anthony T. DiPiazza, Kenneth H. Dinnon, Sayda M. Elbashir, Christine A. Shaw, Angela Woods, Ethan J Fritch, David R. Martinez, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Geoffrey B. Hutchinson, Kapil Bahl, Dario Garcia-Dominguez, LingZhi Ma, Isabella Renzi, Wing-Pui Kong, Stephen D. Schmidt, Lingshu Wang, Yi Zhang, Laura J Stevens, Emily Phung, Lauren A. Chang, Rebecca J. Loomis, Nedim Emil Altaras, Elisabeth Narayanan, Mihir Metkar, Vlad Presnyak, Catherine Liu, Mark K. Louder, Wei Shi, Kwanyee Leung, Eun Sung Yang, Ande West, Kendra L Gully, Nianshuang Wang, Daniel Wrapp, Nicole A. Doria-Rose, Guillaume Stewart-Jones, Hamilton Bennett, Martha C. Nason, Tracy J. Ruckwardt, Jason S. McLellan, Mark R. Denison, James D. Chappell, Ian N Moore, Kaitlyn M. Morabito, John R. Mascola, Ralph S. Baric, Andrea Carfi, Barney Graham
A SARS-CoV-2 vaccine is needed to control the global COVID-19 public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation. ### Competing Interest Statement K.S.C., N.W., J.S.M., and B.S.G. are inventors on International Patent Application No. WO/2018/081318 entitled Prefusion Coronavirus Spike Proteins and Their Use. K.S.C., O.M.A., G.B.H., N.W., D.W., J.S.M, and B.S.G. are inventors on US Patent Application No. 62/972,886 entitled 2019-nCoV Vaccine. R.S.B. filed an invention report for the SARS-CoV-2 MA virus (UNC ref. #18752).
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