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vasculitis and neutrophil extracellular traps in lungs of golden syrian hamsters with sars-cov-2.neutrophil extracellular traps (nets) have been identified as one pathogenetic trigger in severe covid-19 cases and therefore well-described animal models to understand the influence of nets in covid-19 pathogenesis are needed. sars-cov-2 infection causes infection and interstitial pneumonia of varying severity in humans and covid-19 models. pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in covid-19 patients. fur ...202133912167
animal models of covid-19 ii. comparative immunology.developing strong animal models is essential for furthering our understanding of how the immune system functions in response to severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. the alarming speed at which sars-cov-2 has spread, and the high mortality rate of severe coronavirus disease 2019 (covid-19), has required both basic science and clinical research to move at an unprecedented pace. models previously developed to study the immune response against sars-cov have been ra ...202133914873
vascular inflammation is associated with loss of aquaporin 1 expression on endothelial cells and increased fluid leakage in sars-cov-2 infected golden syrian hamsters.vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. the aim of this study was to provide a detailed characterization of the vascular alterations during sars-cov-2 infection and to evaluate the impaired vascular integrity. groups of ten golden syrian hamsters were infected intranasally with sars-cov-2 or phosphate-buffered saline (mock infection) ...202133918079
the pig as a medical model for acquired respiratory diseases and dysfunctions: an immunological perspective.by definition no model is perfect, and this also holds for biology and health sciences. in medicine, murine models are, and will be indispensable for long, thanks to their reasonable cost and huge choice of transgenic strains and molecular tools. on the other side, non-human primates remain the best animal models although their use is limited because of financial and obvious ethical reasons. in the field of respiratory diseases, specific clinical models such as sheep and cotton rat for bronchiol ...202133933817
covid-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (sars-cov-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (covid-19) remains poorly understood. olfactory and taste dysfunction are common in covid-19, especially in mildly symptomatic patients. here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patient ...202133941622
nucleocapsid vaccine elicits spike-independent sars-cov-2 protective immunity.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for the covid-19 pandemic. neutralizing antibodies target the receptor binding domain of the spike (s) protein, a focus of successful vaccine efforts. concerns have arisen that s-specific vaccine immunity may fail to neutralize emerging variants. we show that vaccination with had5 expressing the nucleocapsid (n) protein can establish protective immunity, defined by reduced weight loss and viral load, in both syrian hamst ...202133948591
susceptibility of animal species to experimental sars-cov-2 (coronaviridae: coronavirinae: betacoronavirus; sarbecovirus) infection.due to the new coronavirus infection pandemic, the global scientific community has been forced to change the direction of the most research, focusing on vaccine development as well as the search for new antiviral drugs to treat covid-19. the choice of experimental models, timeframe and approaches for evaluating drugs and vaccines under development is crucial for the development of effective measures to prevent and control this disease.the purpose of this review was to summarize the relevant data ...202133993680
a qualitative igg elisa for detection of sars-cov-2-specific antibodies in syrian hamster serum samples.this protocol describes an indirect enzyme-linked immunosorbent assay for qualitative detection of igg antibodies against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) in syrian hamster serum samples. we describe the preparation of inactivated virus antigens and the negative control antigen and the use of antigen-coated microtiter plates to detect sars-cov-2-specific antibodies from sars-cov-2-infected hamsters, including the criteria for differentiating positive versus negative r ...202133997801
multivalent nanoparticle-based vaccines protect hamsters against sars-cov-2 after a single immunization.the covid-19 pandemic continues to wreak havoc as worldwide sars-cov-2 infection, hospitalization, and death rates climb unabated. effective vaccines remain the most promising approach to counter sars-cov-2. yet, while promising results are emerging from covid-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. here, we engineered the coat protein of the ms2 bacteriophage and generated nanop ...202134011948
inhalable nanobody (pin-21) prevents and treats sars-cov-2 infections in syrian hamsters at ultra-low doses.globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (covid-19). we previously generated the stable and ultrapotent homotrimeric pittsburgh inhalable nanobody 21 (pin-21). using syrian hamsters that model moderate to severe covid-19 disease, we demonstrate the high efficacy of pin-21 to prevent and treat sars-cov-2 infection. intranasal delivery of pin-21 at 0.6 mg/kg protects infected animals from weight loss and substantially reduc ...202134039613
comparing infectivity and virulence of emerging sars-cov-2 variants in syrian hamsters.within one year after its emergence, more than 108 million people acquired sars-cov-2 and almost 2·4 million succumbed to covid-19. new sars-cov-2 variants of concern (voc) are emerging all over the world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. at least three major prototypic voc have been identified, i.e. the united kingdom, uk (b.1.1.7), south african (b.1.351) and brazilian (b.1.1.28.1) variants. the ...202134049240
an immune-competent, replication-permissive syrian hamster glioma model for evaluating delta-24-rgd oncolytic adenovirus.oncolytic adenoviruses are promising new treatments against solid tumors, particularly for glioblastoma (gbm), and preclinical models are required to evaluate the mechanisms of efficacy. however, due to the species selectivity of adenovirus, there is currently no single animal model that supports viral replication, tumor oncolysis, and a virus-mediated immune response. to address this gap, we took advantage of the syrian hamster to develop the first intracranial glioma model that is both adenovi ...202134059921
n-glycolylneuraminic acid in animal models for human influenza a virus.the first step in influenza virus infection is the binding of hemagglutinin to sialic acid-containing glycans present on the cell surface. over 50 different sialic acid modifications are known, of which n-acetylneuraminic acid (neu5ac) and n-glycolylneuraminic acid (neu5gc) are the two main species. animal models with α2,6 linked neu5ac in the upper respiratory tract, similar to humans, are preferred to enable and mimic infection with unadapted human influenza a viruses. animal models that are c ...202134062844
hamster polyomavirus research: past, present, and future.hamster polyomavirus (mesocricetus auratus polyomavirus 1, hapyv) was discovered as one of the first rodent polyomaviruses at the end of the 1960s in a colony of syrian hamsters (mesocricetus auratus) affected by skin tumors. natural hapyv infections have been recorded in syrian hamster colonies due to the occurrence of skin tumors and lymphomas. hapyv infections of syrian hamsters represent an important and pioneering tumor model. experimental infections of syrian hamsters of different colonies ...202134068409
quantitative proteomics of hamster lung tissues infected with sars-cov-2 reveal host factors having implication in the disease pathogenesis and severity.syrian golden hamsters (mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) manifests lung pathology. in this study, efforts were made to check the infectivity of a local sars-cov-2 isolate in a self-limiting and non-lethal hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. the findings of this study confirm the infectivity of this isolate in vivo. analysis of clinical parameters and tissue ...202134105201
prior aerosol infection with lineage a sars-cov-2 variant protects hamsters from disease, but not reinfection with b.1.351 sars-cov-2 variant.the circulation of sars-cov-2 has resulted in the emergence of variants of concern (vocs). it is currently unclear whether the previous infection with sars-cov-2 provides protection against reinfection with vocs. here, we show that low dose aerosol exposure to hcov-19/human/usa/wa-cdc-wa1/2020 (wa1, lineage a), resulted in a productive mild infection. in contrast, a low dose of sars-cov-2 via fomites did not result in productive infection in the majority of exposed hamsters and these animals rem ...202134120579
sars-cov-2 b.1.1.7 infection of syrian hamster does not cause more severe disease, and naturally acquired immunity confers protection.epidemiological studies have revealed the emergence of multiple severe acute respiratory syndrome coronavirus 2 (sars-cov-2) variants of concern (voc), including the lineage b.1.1.7 that is rapidly replacing old variants. the b.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. to assess viral fitness in vivo and to address whether the b.1.1.7 variant is capable of immune escape, we conducted infection and reinfection studies in naive and con ...202134133199
characterization of a new sars-cov-2 variant that emerged in brazil.the spike (s) protein of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) plays a key role in viral infectivity. it is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. recently, a new variant of sars-cov-2 possessing multiple mutations in the s protein, designated p.1, emerged in brazil. here, we characterized a p.1 variant isolated in japan by using syrian hamsters, a well-established small animal mode ...202134140350
western diet increases covid-19 disease severity in the syrian hamster.pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of covid-19. chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a western diet. for the first time in the syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on covid-19 outcome. we observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, ...202134159329
scalable live-attenuated sars-cov-2 vaccine candidate demonstrates preclinical safety and efficacy.successfully combating the covid-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. here, we describe covi-vac, the only live attenuated severe acute respiratory syndrome coronavirus 2 (sars-cov-2) vaccine currently in clinical development. covi-vac was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. in addition, the furin cleavage ...202134193524
nucleocapsid vaccine elicits spike-independent sars-cov-2 protective immunity.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is responsible for the covid-19 pandemic. neutralizing abs target the receptor binding domain of the spike (s) protein, a focus of successful vaccine efforts. concerns have arisen that s-specific vaccine immunity may fail to neutralize emerging variants. we show that vaccination with a human adenovirus type 5 vector expressing the sars-cov-2 nucleocapsid (n) protein can establish protective immunity, defined by reduced weight loss and ...202134193597
sars-cov-2 infects hamster testes.the covid-19 pandemic continues to affect millions of people worldwide. although sars-cov-2 is a respiratory virus, there is growing concern that the disease could cause damage and pathology outside the lungs, including in the genital tract. studies suggest that sars-cov-2 infection can damage the testes and reduce testosterone levels, but the underlying mechanisms are unknown and evidence of virus replication in testicular cells is lacking. we infected golden syrian hamsters intranasally, a mod ...202134204370
potent and protective ighv3-53/3-66 public antibodies and their shared escape mutant on the spike of sars-cov-2.neutralizing antibodies (nabs) to sars-cov-2 hold powerful potentials for clinical interventions against covid-19 disease. however, their common genetic and biologic features remain elusive. here we interrogate a total of 165 antibodies from eight covid-19 patients, and find that potent nabs from different patients have disproportionally high representation of ighv3-53/3-66 usage, and therefore termed as public antibodies. crystal structural comparison of these antibodies reveals they share simi ...202134244522
a single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored sars-cov-2 vaccine protects against pneumonia in hamsters.the development of an effective vaccine against severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the etiologic agent of coronavirus disease 2019 (covid-19), is a global priority. here, we compare the protective capacity of intranasal and intramuscular delivery of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (chimpanzee adenovirus [chad]-sars-cov-2-s) in golden syrian hamsters. although immunization with chad-sars-cov-2-s induces robust spike ...202134245672
sex differences in lung imaging and sars-cov-2 antibody responses in a covid-19 golden syrian hamster model.in the coronavirus disease 2019 (covid-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), more severe outcomes are reported in males than in females, including hospitalizations and deaths. animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of sars-cov-2. adult male and female golden syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 105 50% tissue culture infective dose ...202134253053
single-dose immunization with a chimpanzee adenovirus-based vaccine induces sustained and protective immunity against sars-cov-2 infection.the development of a safe and effective vaccine against sars-cov-2, the causative agent of pandemic coronavirus disease-2019 (covid-19), is a global priority. here, we aim to develop novel sars-cov-2 vaccines based on a derivative of less commonly used rare adenovirus serotype adc68 vector. three vaccine candidates were constructed expressing either the full-length spike (adc68-19s) or receptor-binding domain (rbd) with two different signal sequences (adc68-19rbd and adc68-19rbds). single-dose i ...202134262569
sars-cov-2 infection in the syrian hamster model causes inflammation as well as type i interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney.covid-19 (coronavirus disease 2019) caused by sars-cov-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. a model that captures all clinical symptoms of covid-19 as well as long-haulers disease is needed. we investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after sars-cov-2 infection in syrian hamsters. we found significant increases in infla ...202134265022
preclinical evaluation of imatinib does not support its use as an antiviral drug against sars-cov-2.following the emergence of sars-cov-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. previous reports described the antiviral activity of certain tyrosine kinase inhibitors (tkis) targeting the abelson kinase 2 against pathogenic coronaviruses. imatinib, one of them, has more than twenty years of safe utilization for the treatment of hematological malignancies. in this context, imatinib was rapidly evaluated in clinic ...202134265358
pathogenic and transcriptomic differences of emerging sars-cov-2 variants in the syrian golden hamster model.following the discovery of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and its rapid spread throughout the world, new viral variants of concern (voc) have emerged. there is a critical need to understand the impact of the emerging variants on host response and disease dynamics to facilitate the development of vaccines and therapeutics. syrian golden hamsters are the leading small animal model that recapitulates key aspects of severe coronavirus disease 2019 (covid-19). in this st ...202134268506
sars-cov-2 infection induces the dedifferentiation of multiciliated cells and impairs mucociliary clearance.understanding how sars-cov-2 spreads within the respiratory tract is important to define the parameters controlling the severity of covid-19. here we examine the functional and structural consequences of sars-cov-2 infection in a reconstructed human bronchial epithelium model. sars-cov-2 replication causes a transient decrease in epithelial barrier function and disruption of tight junctions, though viral particle crossing remains limited. rather, sars-cov-2 replication leads to a rapid loss of t ...202134272374
a sars-cov-2 neutralizing antibody selected from covid-19 patients binds to the ace2-rbd interface and is tolerant to most known rbd mutations.the novel betacoronavirus severe acute respiratory syndrome-coronavirus-2 (sars-cov-2) causes a form of severe pneumonia disease called coronavirus disease 2019 (covid-19). to develop human neutralizing anti-sars-cov-2 antibodies, antibody gene libraries from convalescent covid-19 patients were constructed and recombinant antibody fragments (scfv) against the receptor-binding domain (rbd) of the spike protein were selected by phage display. the antibody ste90-c11 shows a subnanometer ic50 in a p ...202134273271
a single dose of replication-competent vsv-vectored vaccine expressing sars-cov-2 s1 protects against virus replication in a hamster model of severe covid-19.the development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the agent responsible for the covid-19 pandemic, is a priority. we designed and produced convac, a replication-competent vesicular stomatitis virus (vsv) vaccine vector that expresses the s1 subunit of sars-cov-2 spike protein. we used golden syrian hamsters as animal models of severe covid-19 to test the efficacy of the convac vaccine. a single vaccine dose elicited high levels of ...202134294728
an enveloped virus-like particle vaccine expressing a stabilized prefusion form of the sars-cov-2 spike protein elicits highly potent immunity.we evaluated enveloped virus-like particles (evlps) expressing various forms of the severe acute respiratory syndrome coronavirus-2 (sars-cov-2) spike protein and several adjuvants in an effort to identify a highly potent coronavirus disease 2019 (covid-19) vaccine candidate. evlps expressing a modified prefusion form of sars-cov-2 spike protein were selected as they induced high antibody binding titers and neutralizing activity after a single injection in mice. formulation of sars-cov-2 s evlps ...202134304928
rethinking remdesivir: synthesis, antiviral activity and pharmacokinetics of oral lipid prodrugs.remdesivir (rdv, gs-5734) is currently the only fda-approved antiviral drug for the treatment of sars cov-2 infection. the drug is approved for use in adults or children 12-years or older who are hospitalized for the treatment of covid-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease. rdv is also unstable in pl ...202134310217
kinetic multi-omic analysis of responses to sars-cov-2 infection in a model of severe covid-19.the host response to sars-cov-2 is poorly understood due to a lack of an animal model that recapitulates severe human disease. here we report a syrian hamster model that develops progressive lethal pulmonary disease that closely mimics severe covid-19. we evaluated host responses using a multi-omic, multi-organ approach to define proteome, phospho-proteome, and transcriptome changes. these data revealed both type i and type ii interferon stimulated gene and protein expression along with a progre ...202134319784
development of safe and highly protective live-attenuated sars-cov-2 vaccine candidates by genome recoding.safe and effective vaccines are urgently needed to stop the pandemic caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). we construct a series of live attenuated vaccine candidates by large-scale recoding of the sars-cov-2 genome and assess their safety and efficacy in syrian hamsters. animals were vaccinated with a single dose of the respective recoded virus and challenged 21 days later. two of the tested viruses do not cause clinical symptoms but are highly immunogenic and ...202134320400
intranasal type i interferon treatment is beneficial only when administered before clinical signs onset in the sars-cov-2 hamster model.impaired type i interferons (ifns) production or signaling have been associated with severe covid-19, further promoting the evaluation of recombinant type i ifns as therapeutics against sars-cov-2 infection. in the syrian hamster model, we show that intranasal administration of ifn-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. by contrast, intranasal administration of ifn-α starting at the onset of symptoms three days post-infecti ...202134370799
ace2-variants indicate potential sars-cov-2-susceptibility in animals: a molecular dynamics study.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) continues to be a global threat, causing millions of deaths worldwide. sars-cov-2 is an enveloped virus with spike (s) glycoproteins conferring binding to the host cell's angiotensin-converting enzyme 2 (ace2), which is critical for cellular entry. the host range of the virus extends well beyond humans and non-human primates. natural and experimental infections have confirmed the high susceptibility of cats, ferrets, and syrian hamster ...202134378348
a methyltransferase-defective vsv-based sars-cov-2 vaccine candidate provides complete protection against sars-cov-2 infection in hamsters.the current pandemic of coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has led to dramatic economic and health burdens. although the worldwide sars-cov-2 vaccination campaign has begun, exploration of other vaccine candidates is needed due to the uncertainties of the current approved vaccines such as durability of protection, cross-protection against variant strains, and costs of long-term production, and storage. in this study, we deve ...202134379509
temporal omics analysis in syrian hamsters unravel cellular effector responses to moderate covid-19.in covid-19, immune responses are key in determining disease severity. however, cellular mechanisms at the onset of inflammatory lung injury in sars-cov-2 infection, particularly involving endothelial cells, remain ill-defined. using syrian hamsters as a model for moderate covid-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from covid-19 patients. monocyte-derived macrophages in lungs exert the earliest and stronges ...202134381043
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