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Currently indexing 100,173 bioRxiv papers from 423,760 authors.

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Results 1 through 20 out of 7924


1: Neuroinvasion of SARS-CoV-2 in human and mouse brain

Eric Song, Ce Zhang et al.

13,237 downloads (posted 26 Jun 2020) microbiology

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2. ### Competing Interest Statement The authors have declared no competing interest.


2: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients

Anthony Levasseur, Jeremy Delerce et al.

12,659 downloads (posted 04 Sep 2020) genomics

The novel coronavirus (SARS-CoV-2) causes pandemic of viral pneumonia. The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between...


3: SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

Aubin Moutal, Laurent F. Martin et al.

10,629 downloads (posted 18 Jul 2020) neuroscience

Global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2’s Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by Spike protei...


4: Long-term survival of salmon-attached SARS-CoV-2 at 4°C as a potential source of transmission in seafood markets

Manman Dai, Huanan Li et al.

7,300 downloads (posted 06 Sep 2020) microbiology

Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. Here we showed that salmon-attached SARS-CoV-2 at 4°C could remain infectious for more than one week, suggesting that fish-attached SARS-CoV-2 may be a source of transmission. ### Competing Interest Statement The authors have declared no competing interest.


5: Jumping back and forth: anthropozoonotic and zoonotic transmission of SARS-CoV-2 on mink farms

Bas B. Oude Munnink, Reina S. Sikkema et al.

5,142 downloads (posted 01 Sep 2020) genomics

The zoonotic origin of the SARS-CoV-2 pandemic is still unknown. Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation of outbreaks on 16 mink farms and humans living or working on these farms, using whole genome sequencing. We conclude that the virus was initially introduced from humans and has evolved, most likely refl...


6: SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients

Juan A Pérez-Bermejo, Serah Kang et al.

4,993 downloads (posted 25 Aug 2020) cell biology

Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural proteins corroborated adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and numerous iPSC-cardiomyocytes lacking nuclear DNA. Human autopsy specimens f...


7: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model

Pamela C. Proud, Daphne Tsitoura et al.

3,991 downloads (posted 25 Sep 2020) immunology

Respiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT h...


8: A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates

Annette B. Vogel, Isis Kanevsky et al.

3,961 downloads (posted 08 Sep 2020) immunology

To contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefus...


9: A Self-Replicating Radiation-Shield for Human Deep-Space Exploration: Radiotrophic Fungi can Attenuate Ionizing Radiation aboard the International Space Station

Graham K. Shunk, Xavier R. Gomez et al.

3,770 downloads (posted 17 Jul 2020) microbiology

The greatest hazard for humans on deep-space exploration missions is radiation. To protect astronauts venturing out beyond Earth’s protective magnetosphere and sustain a permanent presence on Moon and/or Mars, advanced passive radiation protection is highly sought after. Due to the complex nature of space radiation, there is likely no one-size-fits-all solution to this problem, which is further aggravated by up-mass restrictions. In search of innovative radiation-shields, biotechnology holds unique advantages such as su...


10: An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation

Michael Schoof, Bryan Faust et al.

3,748 downloads (posted 10 Aug 2020) biochemistry

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 int...


11: Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences

Alexander Rives, Joshua Meier et al.

3,214 downloads (posted 29 Apr 2019) synthetic biology

In the field of artificial intelligence, a combination of scale in data and model capacity enabled by unsupervised learning has led to major advances in representation learning and statistical generation. In the life sciences, the anticipated growth of sequencing promises unprecedented data on natural sequence diversity. Evolutionary-scale language modeling is a logical step toward predictive and generative artificial intelligence for biology. To this end we use unsupervised learning to train a deep contextual language ...


12: Infection of human lymphomononuclear cells by SARS-CoV-2

Marjorie C Pontelli, Italo A Castro et al.

2,996 downloads (posted 29 Jul 2020) microbiology

Although SARS-CoV-2 severe infection is associated with a hyperinflammatory state, lymphopenia is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection. In this study, SARS-CoV-2 infection of human peripheral blood mononuclear cells (PBMCs) was investigated both in vitro and in vivo . We found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. Re...


13: Topography, spike dynamics and nanomechanics of individual native SARS-CoV-2 virions

Bálint Kiss, Zoltán Kis et al.

2,791 downloads (posted 17 Sep 2020) biophysics

SARS-CoV-2, the virus responsible for the current COVID-19 pandemic, displays a corona-shaped layer of spikes which play fundamental role in the infection process. Recent structural data suggest that the spikes possess orientational freedom and the ribonucleoproteins segregate into basketlike structures. How these structural features regulate the dynamic and mechanical behavior of the native virion, however, remain unknown. By imaging and mechanically manipulating individual, native SARS-CoV-2 virions with atomic force ...


14: Discovery of a Novel Inhibitor of Coronavirus 3CL Protease as a Clinical Candidate for the Potential Treatment of COVID-19

Britton Boras, Rhys M. Jones et al.

2,485 downloads (posted 13 Sep 2020) pharmacology and toxicology

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential to the viral life cycle across a broad spectrum of coronaviruses with no close human analogs. The designed phosphate prodrug PF-07304814 is metabolized to PF-00835321 which is a potent inhibitor in vitro of the coronavirus family 3CL pro, with selectivity over human host protease targets. Furthermore, PF-00835231 exhibits potent in vitro antiviral activity against SARS-CoV-2 as a single agent...


15: Ferrets not infected by SARS-CoV-2 in a high-exposure domestic setting

Kaitlin Sawatzki, Nichola Hill et al.

2,465 downloads (posted 22 Aug 2020) molecular biology

Ferrets ( Mustela putorius furo ) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to SARS-CoV-2 infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic COVID-19. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on RT-PCR and ELISA. To better understand this discrepan...


16: Limited evidence of tumour mutational burden as a biomarker of response to immunotherapy

Carino Gurjao, Dina Tsukrov et al.

2,403 downloads (posted 04 Sep 2020) genomics

Cancer immunotherapy by immune checkpoint blockade (ICB) is effective for several cancer types [1][1], however, its clinical use is encumbered by a high variability in patient response. Several studies have suggested that Tumor Mutational Burden (TMB) correlates with patient response to ICB treatments [2][2]–[6][3], likely due to immunogenic neoantigens generated by novel mutations accumulated during cancer progression [7][4]. Association of TMB and response to checkpoint inhibitors has become widespread in the oncoimmu...


17: Scalable, multimodal profiling of chromatin accessibility and protein levels in single cells

Eleni P. Mimitou, Caleb A. Lareau et al.

2,401 downloads (posted 08 Sep 2020) genomics

Recent technological advances have enabled massively parallel chromatin profiling with single-cell Assay for Transposase Accessible Chromatin by sequencing (scATAC-seq) in thousands of individual cells. Here, we extend these approaches and present ATAC with Select Antigen Profiling by sequencing, ASAP-seq, a tool to simultaneously profile accessible chromatin and protein levels in thousands of single cells. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular prot...


18: SARS-CoV-2 and Malayan pangolin coronavirus infect human endoderm, ectoderm and induced lung progenitor cells

Bixia Hong, Xinyuan Lai et al.

2,261 downloads (posted 25 Sep 2020) microbiology

Since the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several somatic cells, little is known about the infection of SASRS-CoV-2 and its related pangolin coronavirus (GX\_P2V). Here we present for the first time that SARS-CoV-2 pseudovirus and GX\_P2V could infect lung progenitor and even anterior foregut endoderm cells causing these cells death, which differentiated from human embryonic stem cells (hESCs). The infection and replication of SARS-CoV-2 and GX\_P2V were inhibited when treate...


19: Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition

Allison J. Greaney, Tyler N. Starr et al.

2,192 downloads (posted 10 Sep 2020) microbiology

Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and make a major contribution to the neutralizing antibody response elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding, and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even anti...


20: Single-cell profiling of histone modifications in the mouse brain

Marek Bartosovic, Mukund Kabbe et al.

2,063 downloads (posted 03 Sep 2020) neuroscience

The development of the mouse central nervous system (CNS) involves coordinated execution of transcriptional and epigenetic programs. These programs have been extensively studied through single-cell technologies in a pursuit to characterize the underlying cell heterogeneity. However, histone modifications pose additional layers of both positive and negative regulation that defines cellular identity. Here we show that the Cut&Tag technology can be coupled with a droplet-based single cell library preparation platform to pr...