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Currently indexing 125,092 papers from 537,280 authors.

Most downloaded biology preprints, since beginning of last month

Results 1 through 20 out of 3710

in category molecular biology


1: Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease

L. van de Sand, M. Bormann et al.

1,454 downloads (posted 20 Dec 2020)

The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2 in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.


2: The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study

Filip Fratev

1,329 downloads (posted 26 Dec 2020)

The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased;...


3: Evolution of the SARS-CoV-2 proteome in three dimensions (3D) during the first six months of the COVID-19 pandemic

Joseph H. Lubin, Christine Zardecki et al.

987 downloads (posted 01 Dec 2020)

Three-dimensional structures of SARS-CoV-2 and other coronaviral proteins archived in the Protein Data Bank were used to analyze viral proteome evolution during the first six months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48,000 viral proteome sequences showed how each one of the 29 viral study proteins have undergone amino acid changes. Structural models computed for every unique sequence variant revealed t...


4: Simple biochemical features underlie transcriptional activation domain diversity and dynamic, fuzzy binding to Mediator

Adrian L. Sanborn, Benjamin T. Yeh et al.

933 downloads (posted 18 Dec 2020)

Gene activator proteins comprise distinct DNA-binding and transcriptional activation domains (ADs). Because few ADs have been described, we tested domains tiling all yeast transcription factors for activation in vivo and identified 150 ADs. By mRNA display, we showed that 73% of ADs bound the Med15 subunit of Mediator, and that binding strength was correlated with activation. AD-Mediator interaction in vitro was unaffected by a large excess of free activator protein, pointing to a dynamic mechanism of interaction. Struc...


5: Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

Yuancheng Lu, Anitha Krishnan et al.

750 downloads (posted 31 Jul 2019)

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage. Changes to DNA methylation patterns over time form the basis of an 'ageing clock', but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the centr...


6: A rapid, highly sensitive and open-access SARS-CoV-2 detection assay for laboratory and home testing

Max J. Kellner, James J Ross et al.

707 downloads (posted 23 Jun 2020)

Global efforts to combat the Covid-19 pandemic caused by the beta coronavirus SARS-CoV-2 are currently based on RT-qPCR-based diagnostic tests. However, their high cost, moderate throughput and reliance on sophisticated equipment limit widespread implementation. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative detection method that has the potential to overcome these limitations. Here we present a rapid, robust, highly sensitive and versatile RT-LAMP based SARS-CoV-2 detecti...


7: A comparison of DNA stains and staining methods for Agarose Gel Electrophoresis

Andie C. Hall

684 downloads (posted 06 Mar 2019)

Nucleic acid stains are necessary for Agarose Gel Electrophoresis (AGE). The commonly used but mutagenic Ethidium Bromide is being usurped by a range of safer but more expensive alternatives. These safe stains vary in cost, sensitivity and the impedance of DNA as it migrates through the gel. Modified protocols developed to reduce cost increase this variability. In this study, five Gel stains (GelRed™, GelGreen™, SYBR™ safe, SafeView and EZ-Vision®In-Gel Solution) two premixed loading dyes (SafeWhite, EZ-Vision®One) and ...


8: In Vitro Analysis of the Anti-viral Potential of nasal spray constituents against SARS-CoV-2

Mark L Cannon, Jonna B. Westover et al.

646 downloads (posted 03 Dec 2020)

Viral pandemics have taken a significant toll on humanity and the world now is contending with the SARS-CoV-2 epidemic. Readily available economical preventive measures should be immediately explored. Xylitol has been reported to reduce the severity of viral infections as well as the severity of pneumonia, and increase the survivability of animal subjects. Since pneumonia and acute respiratory distress syndrome are potentially fatal complications of COVID-19, the present study tested the in vitro effectiveness of xylito...


9: Structural basis for piRNA-targeting

Todd A. Anzelon, Saikat Chowdhury et al.

519 downloads (posted 07 Dec 2020)

Piwi proteins use PIWI-interacting RNAs (piRNAs) to identify and silence the transposable elements (TEs) pervasively found in animal genomes. The Piwi targeting mechanism is proposed to be similar to targeting by Argonaute proteins, which employ microRNA (miRNA) guides to repress cellular mRNAs, but has not been characterized in detail. We present cryo-EM structures of a Piwi-piRNA complex with and without target RNAs and analysis of target recognition. Resembling Argonaute, Piwi identifies targets using the piRNA seed-...


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

Kaitlin Sawatzki, Nichola Hill et al.

509 downloads (posted 22 Aug 2020)

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...


11: Single-cell intracellular epitope and transcript detection revealing signal transduction dynamics

Francesca Rivello, Erik van Buijtenen et al.

481 downloads (posted 02 Dec 2020)

Current high-throughput single-cell multi-omics methods cannot concurrently map changes in (phospho)protein levels and the associated gene expression profiles. We present QuRIE-seq (Quantification of RNA and Intracellular Epitopes by sequencing) and use multi-factor omics analysis (MOFA+) to map signal transduction over multiple timescales. We demonstrate that QuRIE-seq can trace the activation of the B-cell receptor pathway at the minute and hour time-scale and provide insight into the mechanism of action of an inhibit...


12: Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation

Tingting Li, Qingbing Zheng et al.

446 downloads (posted 17 Mar 2020)

Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins—receptor binding domain (RBD), S1 subunit and S ectodomain—in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent ...


13: The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

Markus Hoffmann, Hannah Kleine-Weber et al.

444 downloads (posted 31 Jan 2020)

The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inh...


14: Enabling high-accuracy long-read amplicon sequences using unique molecular identifiers with Nanopore or PacBio sequencing

Søren M Karst, Ryan M. Ziels et al.

441 downloads (posted 24 May 2019)

High-throughput amplicon sequencing of large genomic regions remains challenging for short-read technologies. Here, we report a high-throughput amplicon sequencing approach combining unique molecular identifiers (UMIs) with Oxford Nanopore Technologies or Pacific Biosciences CCS sequencing, yielding high accuracy single-molecule consensus sequences of large genomic regions. Our approach generates amplicon and genomic sequences of >10,000 bp in length with a mean error-rate of 0.0049-0.0006% and chimera rate <0.022%.


15: Validation of a Lysis Buffer Containing 4 M Guanidinium Thiocyanate (GITC)/ Triton X-100 for Extraction of SARS-CoV-2 RNA for COVID-19 Testing: Comparison of Formulated Lysis Buffers Containing 4 to 6 M GITC, Roche External Lysis Buffer and Qiagen RTL Lysis Buffer

Martina F Scallan, Catherine Dempsey et al.

434 downloads (posted 08 Apr 2020)

The COVID-19 pandemic has resulted in increased need for diagnostic testing using reverse transcriptase real-time PCR (RT-PCR). An exponential increase in demand has resulted in a shortage of numerous reagents in particular those associated with the lysis buffer required to extract the viral RNA. Herein, we describe a rapid collective effort by hospital laboratory scientists, academic researchers and the biopharma industry to generate a validated lysis buffer. We have formulated a 4M Guanidinium thiocyanate (GITC)/ Trit...


16: Performance comparison of reverse transcriptases for single-cell studies

Zucha Daniel, Androvic Peter et al.

424 downloads (posted 07 May 2019)

Background: Recent technical advances allowing quantification of RNA from single cells are revolutionizing biology and medicine. Currently, almost all single-cell transcriptomic protocols rely on conversion of RNA to cDNA by reverse transcription (RT). However, RT is recognized as highly limiting step due to its inherent variability and suboptimal sensitivity, especially at minute amounts of RNA. Primary factor influencing RT outcome is reverse transcriptase (RTase). Recently, several new RTases with potential to decrea...


17: An ultrasensitive, rapid, and portable coronavirus SARS-CoV-2 sequence detection method based on CRISPR-Cas12

Curti Lucia, Pereyra-Bonnet Federico et al.

393 downloads (posted 02 Mar 2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has received global attention due to the recent outbreak in China. In this work, we report a CRISPR-Cas12 based diagnostic tool to detect synthetic SARS-CoV-2 RNA sequences in a proof-of-principle evaluation. The test proved to be sensitive, rapid, and potentially portable. These key traits of the CRISPR method are critical for virus detection in regions that lack resources to use the currently available methods.


18: Substrate-engaged type III secretion system structures reveal gating mechanism for unfolded protein translocation

Sean Miletic, Dirk Fahrenkamp et al.

390 downloads (posted 18 Dec 2020)

Many bacterial pathogens strictly rely on the activity of type III secretion systems (T3SSs) to secrete and translocate effector proteins in order to establish infection. The central component of T3SSs is the needle complex, a supramolecular machine which assembles a continuous conduit crossing the bacterial envelope and the host cell membrane to allow bacterial effectors to gain entry into the host cell cytoplasm to modulate signal transduction processes. Disruption of this process impairs pathogenicity, providing an a...


19: One-step RNA extraction for RT-qPCR detection of 2019-nCoV

Monica Sentmanat, Evguenia Kouranova et al.

377 downloads (posted 05 Apr 2020)

The global outbreak of coronavirus disease 2019 (COVID-19) has placed an unprecedented burden on healthcare systems as the virus spread from the initial 27 reported cases in the city of Wuhan, China to a global pandemic in under three month[1]. Resources essential to monitoring virus transmission have been challenged with a demand for expanded surveillance. The CDC 2019-nCoV Real-Time Diagnostic Panel uses a real-time reverse transcription polymerase chain reaction (RT-PCR) consisting of two TaqMan probe and primer sets...


20: Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

Daniel J Butler, Christopher Mozsary et al.

346 downloads (posted 20 Apr 2020)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale sho...