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| Open AccessCross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C
The antibody response to the SARS-CoV-2 Omicron variant is not well studied in children. Here, the authors provide an age-stratified analysis of SARS-CoV-2 neutralizing capacity of sera from children with acute or convalescent COVID-19 as well as children with multisystem inflammatory syndrome.
- Juanjie Tang
- , Tanya Novak
- & Surender Khurana
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Article
| Open AccessStructural basis for broad anti-phage immunity by DISARM
DISARM (Defense Island System Associated with Restriction Modification) systems can provide bacteria with protection against a wide range of phage. Here, Bravo et al. determine cryo-EM structures of the core DISARM complex that shed light onto phage DNA recognition and activation of this widespread defense system.
- Jack P. K. Bravo
- , Cristian Aparicio-Maldonado
- & David W. Taylor
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Article
| Open AccessImproving recombinant protein production by yeast through genome-scale modeling using proteome constraints
Due to the complexity of the protein secretory pathway, strategy suitable for the production of a certain recombination protein cannot be generalized. Here, the authors construct a proteome-constrained genome-scale protein secretory model for yeast and show its application in the production of different misfolded or recombinant proteins.
- Feiran Li
- , Yu Chen
- & Jens Nielsen
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Article
| Open AccessCross-neutralization of Omicron BA.1 against BA.2 and BA.3 SARS-CoV-2
It is important to understand the cross-neutralization among distinct SARS-CoV-2 Omicron sublineages. Zou et al. show that sera from Omicron BA.1-infected people are significantly weaker in neutralizing Omicron BA.2, BA.3, and USA-WA1/2020 than neutralizing BA.1.
- Jing Zou
- , Chaitanya Kurhade
- & Pei-Yong Shi
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Article
| Open AccessSARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5
SERINC5, is a cellular multipass transmembrane protein involved in sphingolipid and phosphatydilserine biogenesis and a known retroviral restriction factor. Here, Timilsina et al. show that SERINC5 is a host restriction factor for SARS-CoV-2 that prevents viral fusion during entry. Further they show that viral ORF7a counteracts SERINC5 anti-viral activity by blocking its incorporation into progeny virions.
- Uddhav Timilsina
- , Supawadee Umthong
- & Spyridon Stavrou
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Article
| Open AccessTransgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission
Plasmodium gametes and sporozoites activate surface-bound plasminogen to plasmin that degrades extracellular matrix barriers, therewith facilitating parasite motility in mosquitoes and mammalian hosts. To control malaria transmission, Pascini et al. generate Anopheles stephensi transgenic mosquitoes constitutively secreting human plasminogen activator inhibitor 1 in midgut and/or saliva which leads to inhibition of plasminogen activation and a reduction in oocyst intensity, infection prevalence, and transmission.
- Tales V. Pascini
- , Yeong Je Jeong
- & Joel Vega-Rodríguez
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Article
| Open AccessInsights into methionine S-methylation in diverse organisms
S-methyl methionine (SMM) is a key molecule in production of dimethylsulfoniopropionate (DMSP), an important marine anti-stress compound, with roles in global nutrient cycling. Here, the authors determine the mechanism of SMM synthesis and uncover unexpected roles for SMM in archaea, CPR bacteria and animals.
- Ming Peng
- , Chun-Yang Li
- & Yu-Zhong Zhang
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Article
| Open AccessCombining rapid antigen testing and syndromic surveillance improves community-based COVID-19 detection in a low-income country
Rapid antigen tests and syndromic surveillance for identification of COVID-19 cases are limited by low sensitivity and specificity, respectively. Here, the authors use data from Bangladesh and show that combining the two methods improves diagnostic accuracy in a range of epidemiological scenarios.
- Fergus J. Chadwick
- , Jessica Clark
- & Ayesha Sania
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Article
| Open AccessBiogenesis of a bacterial metabolosome for propanediol utilization
Bacteria have evolved proteinaceous microcompartments (BMCs) to control the passage of metabolites and facilitate catabolism in a micro-environment. Here, Yang et al. apply fluorescence microscopy to characterize the protein-protein interaction and assembly involved in the de novo biogenesis of propanediol-utilization (Pdu) metabolosomes and show that Pdu BMCs undergo a combination of ‘Shell first’ and ‘Cargo first’ assembly.
- Mengru Yang
- , Nicolas Wenner
- & Lu-Ning Liu
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Article
| Open AccessAntigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes
Human coronavirus OC43 causes respiratory disease and is maintained in the human population through recurring infections. Here, by extensive structural analyses, the authors provide insights into the binding sites and breadth of neutralizing antibodies against this endemic coronavirus.
- Chunyan Wang
- , Emma L. Hesketh
- & Berend-Jan Bosch
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Article
| Open AccessSeeking patterns of antibiotic resistance in ATLAS, an open, raw MIC database with patient metadata
Pathogens are typically classified as ‘antibiotic-resistant’ for clinical purposes based on cut-off values of minimum inhibitory concentrations (MICs). In this study, the authors explore quantitative values of MICs using the global ‘ATLAS’ database of pathogen-antibiotic pairs, describe trends in resistance, and compare results to other antibiotic resistance surveillance data.
- Pablo Catalán
- , Emily Wood
- & Robert E. Beardmore
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Article
| Open AccessThe RNA-bound proteome of MRSA reveals post-transcriptional roles for helix-turn-helix DNA-binding and Rossmann-fold proteins
RNA-binding proteins play key roles in controlling gene expression in many organisms. Here, Chu et al. identify hundreds of RNA-binding proteins in methicillin-resistant Staphylococcus aureus, and show that a major transcription factor uses its helix-turn-helix domain to bind RNAs near intrinsic transcription terminators.
- Liang-Cui Chu
- , Pedro Arede
- & Sander Granneman
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Article
| Open AccessCompetent immune responses to SARS-CoV-2 variants in older adults following two doses of mRNA vaccination
mRNA-based SARS-CoV-2 vaccines can induce protective immunity in older individuals, but whether they encompass new variants is not clear. Here the authors assess mRNA vaccine responses in both younger (<50) and older (>55) cohorts to find slightly delayed humoral and cellular immunity in the latter but, more importantly, reactivity to multiple variants.
(I understand an eTOC summary is provided, but unfortunately it does not conform with our format.)
- Mladen Jergović
- , Jennifer L. Uhrlaub
- & Janko Nikolich-Žugich
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Article
| Open AccessPredicting cancer prognosis and drug response from the tumor microbiome
Computational approaches have been developed to estimate tumor microbial abundances from whole genomic and RNA-sequencing datasets. Here the authors report the predictive value of tumor microbial abundance, alone or in combination with gene expression data, for cancer prognosis and drug response.
- Leandro C. Hermida
- , E. Michael Gertz
- & Eytan Ruppin
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Article
| Open AccessAn in vivo gene amplification system for high level expression in Saccharomyces cerevisiae
Gene dosage-based expression upregulation suffers from instability and random gene integration. Here, the authors report HapAmp, a method that uses haploinsufficiency as evolutionary force to drive in vivo gene amplification, and demonstrate its applications in protein and biochemical production in yeast.
- Bingyin Peng
- , Lygie Esquirol
- & Claudia E. Vickers
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Article
| Open AccessOff-season RSV epidemics in Australia after easing of COVID-19 restrictions
Non-pharmaceutical interventions for COVID-19 also reduced incidence of respiratory pathogens such as respiratory syncytial virus (RSV). Here, the authors report the resurgence of RSV in Australia following lifting of some of the restrictions and describe reduction in genetic diversity in circulating clades.
- John-Sebastian Eden
- , Chisha Sikazwe
- & Tyna Tran
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Article
| Open AccessStructural insights into the mechanism of archaellar rotational switching
Signal transduction via phosphorylated CheY is conserved in bacteria and archaea. In this study, the authors employ structural biochemistry combined with cell biology to delineate the mechanism of CheY recognition by the adaptor protein CheF.
- Florian Altegoer
- , Tessa E. F. Quax
- & Gert Bange
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Article
| Open AccessDynamic character displacement among a pair of bacterial phyllosphere commensals in situ
In this study, the concept of dynamic character displacement among interacting bacterial species from leaf-colonizing families was empirically tested using a proteomics approach. A phenotypic shift towards the utilization of alternative carbon sources was observed during coexistence, thereby minimizing niche overlap.
- Lucas Hemmerle
- , Benjamin A. Maier
- & Julia A. Vorholt
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Article
| Open AccessA truncated anti-CRISPR protein prevents spacer acquisition but not interference
Phages can use ACR proteins that inhibit the adaptive immunity activities of bacterial CRISPR-Cas systems. Here, Philippe et al. show that these systems can block ACR-containing phages by targeting the acr gene, and this can select for phage mutants carrying a deletion within acr that does not block DNA cleavage (interference) but prevents the addition of new immunity (spacer acquisition).
- Cécile Philippe
- , Carlee Morency
- & Sylvain Moineau
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Article
| Open AccessFrequency modulation of a bacterial quorum sensing response
Quorum-sensing bacteria produce and secrete autoinducers that trigger a behavioral change in the population when reaching a certain threshold. Here, Bettenworth et al. show that autoinducer synthase gene expression in Sinorhizobium meliloti occurs in asynchronous stochastic pulses, and that physiological cues modulate pulse frequency and, consequently, response behavior dynamics. Frequency-modulated pulsing in autoinducer synthase gene expression thus represents a time-based mechanism for information integration and collective decision-making.
- Vera Bettenworth
- , Simon van Vliet
- & Anke Becker
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Article
| Open AccessSARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity
The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.
- Wuji Zhang
- , Brendon Y. Chua
- & Katherine Kedzierska
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Article
| Open AccessElimination of human rabies in Goa, India through an integrated One Health approach
Dog vaccination is an effective rabies prevention measure, but widespread vaccination campaigns are challenging in settings like India with large free-roaming dog populations. Here, the authors describe a One Health campaign in Goa state which led to a large reduction of cases in dogs and elimination in humans.
- A. D. Gibson
- , G. Yale
- & R. J. Mellanby
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Article
| Open AccessBroad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro
A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here the authors show that CRISPR-Cas13d can be used as a broad-spectrum antiviral to inhibit human coronaviruses, including new SARS-CoV-2 variants, combined with small molecule drugs for an enhanced antiviral effect in human primary cells.
- Leiping Zeng
- , Yanxia Liu
- & Lei S. Qi
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Article
| Open AccessCo-infection with SARS-CoV-2 Omicron and Delta variants revealed by genomic surveillance
Here, using genomic approaches, Rockett et al. identify Omicron and Delta SARS-CoV-2 co-infections in two adults, highlighting the usefulness of genomic surveillance for the timely recognition of co-infections in situations when different variants of the virus are circulating in the community.
- Rebecca J. Rockett
- , Jenny Draper
- & Vitali Sintchenko
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Article
| Open AccessOrigins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation
Streptococcal siglec-like binding regions (SLBRs) selectively bind cell surface glycans, but the basis for this selectivity is not understood. Here, the authors identify selectivity-modulating SLBR regions and study how changes in SLBR glycan selectivity affect interactions with human glycoprotein receptors.
- Barbara A. Bensing
- , Haley E. Stubbs
- & T. M. Iverson
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Article
| Open AccessMineralogical control on methylotrophic methanogenesis and implications for cryptic methane cycling in marine surface sediment
Adsorption of methylamines onto clay minerals provides a hitherto unrecognised control on methane production in marine surface sediment.
- Ke-Qing Xiao
- , Oliver W. Moore
- & Caroline L. Peacock
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Comment
| Open AccessLearnings from Thailand in building strong surveillance for malaria elimination
On the cusp of Plasmodium falciparum (Pf) elimination, Thailand is accelerating towards zero malaria by 2024. This commentary reviews the heart of its success—effective surveillance—and what else may be needed to reach zero on time.
- Jui A. Shah
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Comment
| Open AccessTackling malaria transmission at a single cell level in an endemic setting in sub-Saharan Africa
Studying malaria transmission biology using scRNA-sequencing provides information on within-host strain diversity and transcriptional states. Here, we comment on our collaborative efforts at establishing single-cell capacities in sub-Saharan Africa and the challenges encountered in Mali’s endemic setting.
- Antoine Dara
- , Sunil Kumar Dogga
- & Mara K. N. Lawniczak
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Comment
| Open AccessMalaria in 2022: Increasing challenges, cautious optimism
Malaria cases and deaths remain unacceptably high and are resurgent in several settings, though recent developments inspire optimism. This includes the approval of the world’s first malaria vaccine and results from novel vaccine candidates and trials testing innovative combinatorial interventions.
- Prasanna Jagannathan
- & Abel Kakuru
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Comment
| Open AccessA broader perspective on the economics of malaria prevention and the potential impact of SARS-CoV-2
Economic evaluations of public health interventions to prevent malaria should consider the adoption of wider perspectives and the inclusion of non-health impacts, particularly economic development outcomes, such as education. This is especially relevant in malaria elimination settings and in the context of the current SARS-CoV-2 pandemic.
- Elisa Sicuri
- , Francesco Ramponi
- & Francisco Saúte
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Article
| Open AccessQuadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants
Emerging SARS-CoV-2 variants with multiple mutations raise concerns on vaccine effectiveness. Here, Kang et al. report that a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and three different VOCs confer protection against SARS-CoV-2 variants in mice.
- Yin-Feng Kang
- , Cong Sun
- & Mu-Sheng Zeng
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Article
| Open AccessHeterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant
Emerging SARS-CoV-2 variants of concern (VOCs) raises concerns regarding vaccine efficacy. Here, the authors evaluate the neutralizing antibody, and cellular response elicited following inactivated vaccine immunization, and mRNA booster, against the Omicron variant.
- Fanglei Zuo
- , Hassan Abolhassani
- & Qiang Pan-Hammarström
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Article
| Open AccessGenomic diversity across the Rickettsia and ‘Candidatus Megaira’ genera and proposal of genus status for the Torix group
The bacterial genus Rickettsia includes vector-borne pathogens and arthropod symbionts that are close relatives of symbionts of microeukaryotes classified under the genus ‘Candidatus Megaira’. Here, Davison et al. clarify the evolutionary relationships between these organisms by assembling 28 genomes of understudied species, and propose that a distinct clade known as Torix Rickettsia should be considered a separate genus.
- Helen R. Davison
- , Jack Pilgrim
- & Stefanos Siozios
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Article
| Open AccessLarge differences in carbohydrate degradation and transport potential among lichen fungal symbionts
Lichen symbioses are thought to be stabilized by the transfer of fixed carbon from a photosynthesizing symbiont to a fungus. Here, Resl et al. show that, contrary to other fungal symbioses, fungal association with a phototroph in lichens does not result in loss of fungal enzymes for plant cell-wall degradation.
- Philipp Resl
- , Adina R. Bujold
- & Toby Spribille
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Matters Arising
| Open AccessReply to: Testing the adaptive hypothesis of lagging-strand encoding in bacterial genomes
- Houra Merrikh
- & Christopher Merrikh
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Matters Arising
| Open AccessTesting the adaptive hypothesis of lagging-strand encoding in bacterial genomes
- Haoxuan Liu
- & Jianzhi Zhang
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Article
| Open AccessIn vitro reconstitution of Escherichia coli divisome activation
In E. coli, FtsA and FtsZ control the place and time of cell division. Here, the authors use in vitro experiments to show how FtsA can follow FtsZ treadmilling and that downstream proteins form dynamic copolymers with FtsA to initiate division.
- Philipp Radler
- , Natalia Baranova
- & Martin Loose
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Article
| Open AccessDeep learning of a bacterial and archaeal universal language of life enables transfer learning and illuminates microbial dark matter
Computational methods to analyse microbial systems rely on reference databases which do not capture their full functional diversity. Here the authors develop a deep learning model and apply it using transfer learning, creating biologically useful models for multiple different tasks.
- A. Hoarfrost
- , A. Aptekmann
- & Y. Bromberg
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Article
| Open AccessUnlocking the functional potential of polyploid yeasts
Domesticated industrial yeast strains are sterile, which hampers to breed strains with novel properties. Here, the authors employ the genetics paradigm return-to-growth to induce genome wide recombination in two sterile polyploid industrial yeasts and identify clones with superior biotechnological traits.
- Simone Mozzachiodi
- , Kristoffer Krogerus
- & Gianni Liti
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Article
| Open AccessImmunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation
Human cytomegalovirus is a major cause of morbidity and mortality in transplant patients and multiple immune cells types are critical during infection and reactivation. Here the authors assess the immune cell compartments of haematopoietic stem cell recipients in the early period post transplantation and identify key features of effector memory CD4+ T cells and mucosal associated invariant T cells in this context.
- Lauren Stern
- , Helen M. McGuire
- & Barry Slobedman
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Article
| Open AccessProspective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
Clinical studies have suggested that the therapeutic potential of polyclonal convalescent plasma is highest in the first days of symptoms. Here, the authors present results from a pooled analysis of two clinical trials in COVID-19 outpatients that did not provide conclusive evidence in favor of convalescent plasma.
- Pere Millat-Martinez
- , Arvind Gharbharan
- & Michael Marks
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Article
| Open AccessOff-the-shelf CAR natural killer cells secreting IL-15 target spike in treating COVID-19
Severe COVID-19 requires immediate and targeted intervention that is efficient against SARS-CoV-2 and its variants. Authors show here the therapeutic potential of engineered natural killer cells that simultaneously express a chimeric antigen receptor targeting the spike protein of SARS-CoV-2, and IL-15, a cytokine that enhances the function and survival of their own.
- Ting Lu
- , Rui Ma
- & Jianhua Yu
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Article
| Open AccessSystematic and quantitative view of the antiviral arsenal of prokaryotes
Bacteria and archaea have developed multiple antiviral mechanisms. Here, Tesson et al. present a tool that automatically detects known antiviral systems in prokaryotic genomes, and show that variations in antiviral strategies correlate with genome size, viral threat, and lifestyle traits.
- Florian Tesson
- , Alexandre Hervé
- & Aude Bernheim
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Article
| Open AccessSystematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy
Pregnant women have been disproportionately under-vaccinated against COVID-19, partly because they were excluded from initial trials. This systematic review and meta-analysis supports efficacy of vaccination in pregnancy, and finds no evidence of adverse maternal or perinatal outcomes.
- Smriti Prasad
- , Erkan Kalafat
- & Asma Khalil
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Article
| Open AccessCumulative SARS-CoV-2 mutations and corresponding changes in immunity in an immunocompromised patient indicate viral evolution within the host
Variants of concerns arise from SARS-CoV-2 mutations poise as severe public health threats. Here the authors chronicle SARS-CoV-2 mutations onset and immune parameters in an immunocompromised patient with continuous virus-shedding, thereby hinting potential intra-host viral evolution and escape facilitated by ineffective T cell immunity.
- Sissy Therese Sonnleitner
- , Martina Prelog
- & Gernot Walder
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Article
| Open AccessArchival influenza virus genomes from Europe reveal genomic variability during the 1918 pandemic
For archival pathogens, like pH1N1 Influenza A virus the causative agent of 1918/19 pandemic, only few whole genome sequences exist. Here, Patrono et al. provide one complete and two partial genomes from Germany and find variation in two sites in the nucleoprotein gene in pandemic samples compared to pre-pandemic samples, that are associated with resistance to host antiviral response, pointing at a possible viral adaptation to humans.
- Livia V. Patrono
- , Bram Vrancken
- & Sébastien Calvignac-Spencer
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Article
| Open AccessMultivalent 9-O-Acetylated-sialic acid glycoclusters as potent inhibitors for SARS-CoV-2 infection
Cell surface attachment factors, such as glycans, play an important role in viral infection. Here, Petitjean et al. show that SARS-CoV-2 specifically binds to 9-Oacetylated sialic acid and have designed novel inhibitors based on multivalent derivatives.
- Simon J. L. Petitjean
- , Wenzhang Chen
- & David Alsteens
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Article
| Open AccessProfiling of hMPV F-specific antibodies isolated from human memory B cells
Here, Xiao et al. isolate a large panel of antibodies against human metapneumovirus fusion protein from human B cells, and characterize their epitopes, neutralization activities, and antigen binding specificity, providing a useful framework for understanding the immune response against hMPV.
- Xiao Xiao
- , Arthur Fridman
- & Lan Zhang
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Article
| Open AccessA randomized controlled trial for response of microbiome network to exercise and diet intervention in patients with nonalcoholic fatty liver disease
Exercise and diet interventions are treatments for nonalcoholic fatty liver disease (NAFLD). Here the authors report that in randomized, controlled trial in patients with NAFLD exercise and diet intervention were associated with diversified gut microbiome keystone taxa. Exploratory analysis suggests gut microbial network may be used to predict the individual liver fat response to exercise intervention, if validated in future studies.
- Runtan Cheng
- , Lu Wang
- & Sulin Cheng
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