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monitoring of sars-cov-2 infection in mustelids.american mink and ferret are highly susceptible to severe acute respiratory syndrome coronavirus 2 (sars-cov-2), but no information is available for other mustelid species. sars-cov-2 spreads very efficiently within mink farms once introduced, by direct and indirect contact, high within-farm animal density increases the chance for transmission. between-farm spread is likely to occur once sars-cov-2 is introduced, short distance between sars-cov-2 positive farms is a risk factor. as of 29 january ...202133717355
lack of molecular mimicry between nonhuman primates and infectious pathogens: the possible genetic bases.recently, it was found that proteomes from poliovirus, measles virus, dengue virus, and severe acute respiratory syndrome-related coronavirus 2 (sars-cov-2) have high molecular mimicry at the heptapeptide level with the human proteome, while heptapeptide commonality is minimal or absent with proteomes from nonhuman primates, that is, gorilla, chimpanzee, and rhesus macaque. to acquire more data on the issue, analyses here have been expanded to ebola virus, francisella tularensis , human immunode ...202133748822
a single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against sars-cov-2 infection in rhesus macaques.the deployment of a vaccine that limits transmission and disease likely will be required to end the coronavirus disease 2019 (covid-19) pandemic. we recently described the protective activity of an intranasally administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (s) protein (chad-sars-cov-2-s [chimpanzee adenovirus-severe acute respiratory syndrome-coronavirus-2-s]) in the upper and lower respiratory tracts of mice expressing the human angiotensin-convertin ...202133754147
experimental sars-cov-2 infection of bank voles.after experimental inoculation, severe acute respiratory syndrome coronavirus 2 infection was confirmed in bank voles by seroconversion within 8 days and detection of viral rna in nasal tissue for up to 21 days. however, transmission to contact animals was not detected. thus, bank voles are unlikely to establish effective transmission cycles in nature.202133754987
epidemiological study of betacoronaviruses in captive malayan pangolins.the coronavirus disease 2019 (covid-19) outbreak has significantly affected international public health safety. it has been reported that the pathogen severe acute respiratory syndrome coronavirus 2 (sars-cov-2), which causes covid-19, could originate from bats and utilize the malayan pangolin (manis javanica) as an intermediate host. to gain further insights into the coronaviruses carried by pangolins, we investigated the occurrence of betacoronavirus (β-cov) infections in captive malayan pango ...202133763052
inactivated rabies virus vectored sars-cov-2 vaccine prevents disease in a syrian hamster model.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is an emergent coronavirus that has caused a worldwide pandemic. although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. there is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. here we further evaluated an inactivated rabies vectored sars-cov-2 s1 vaccine coravax in a syrian hamste ...202133765062
development of a colloidal gold-based immunochromatographic strip for rapid detection of severe acute respiratory syndrome coronavirus 2 spike protein.the outbreak and worldwide pandemic of the novel severe acute respiratory syndrome coronavirus 2 (sars-cov-2) have a significant impact on global economy and human health. in order to reduce the disease spread, 16 monoclonal antibodies (mcabs) again sars-cov-2 were generated by immunized mice with the spike protein receptor binding domain (rbd), which was expressed in chinese hamster ovary cell (cho). a colloidal gold-based immunochromatographic strip was developed with two mcabs to detect sars- ...202133777026
detection and genome sequencing of sars-cov-2 in a domestic cat with respiratory signs in switzerland.since the emergence of coronavirus disease (covid-19) in late 2019, domestic cats have been demonstrated to be susceptible to severe acute respiratory syndrome coronavirus-2 (sars-cov-2) under natural and experimental conditions. as pet cats often live in very close contact with their owners, it is essential to investigate sars-cov-2 infections in cats in a one-health context. this study reports the first sars-cov-2 infection in a cat in a covid-19-affected household in switzerland. the cat (cat ...202133802899
sars-cov-2 infection and antibody response in a symptomatic cat from italy with intestinal b-cell lymphoma.since the coronavirus disease (covid-19) pandemic was first identified in early 2020, rare cases of severe acute respiratory syndrome coronavirus-2 (sars-cov-2) infection in pet cats have been reported worldwide. some reports of cats with sars-cov-2 showed self-limiting respiratory or gastrointestinal disease after suspected human-to-feline transmission via close contact with humans with sars-cov-2. in the present study, we investigated a cat with sars-cov-2 that was presented to a private anima ...202133806922
covid-19 pandemic: what about the safety of anti-coronavirus nanoparticles?every day, new information is presented with respect to how to best combat the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). this manuscript sheds light on such recent findings, including new co-factors (i.e., neuropilin-1) and routes (i.e., olfactory transmucosal) allowing cell entry of sars-cov-2 and induction of neurological symptoms, as well as the new sars-cov-2 variants. we highlight the sars-cov-2 human-animal interfaces and elaborate containment strategies using the same ...202133808934
the neutralizing antibody, ly-cov555, protects against sars-cov-2 infection in nonhuman primates.severe acute respiratory syndrome coronavirus-2 (sars-cov-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. here, we report that high-throughput microfluidic screening of antigen-specific b cells led to the identification of ly-cov555 (also known as bamlanivimab), a pot ...202133820835
sex differences in lung imaging and sars-cov-2 antibody responses in a covid-19 golden syrian hamster model.in the ongoing 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 compared with 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 (8-10 weeks of age) were inoculated intranasally with 10 5 tcid 50 of sars-cov-2/ ...202133821269
animal models of covid-19. i. comparative virology and disease pathogenesis.the coronavirus disease 2019 (covid-19) pandemic has fueled unprecedented development of animal models to understand disease pathogenesis, test therapeutics, and support vaccine development. models previously developed to study severe acute respiratory syndrome coronavirus (sars-cov) have been rapidly deployed to study sars-cov-2. however, it has become clear that despite the common use of ace2 as a receptor for both viruses, the host range of the 2 viruses does not entirely overlap. distinct ac ...202133836527
preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) continue at pace. here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (s) protein, sclamp, in combination with the licensed adjuvant mf59 'mf59c.1' (seqirus, parkville, australia).202133841880
sars-cov-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses.the outbreak and spread of sars-cov-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. the spike glycoprotein of sars-cov-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. here, we show that adjuvanted protein immunization with soluble sars-cov-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, wit ...202133842900
host barriers to sars-cov-2 demonstrated by ferrets in a high-exposure domestic setting.ferrets (mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (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 disease, one of whom was confirmed positive for sars-cov-2. we observed n ...202133858941
structural and functional characterization of sars-cov-2 rbd domains produced in mammalian cells.as the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) pandemic is still ongoing and dramatically influences our life, the need for recombinant viral proteins for diagnostics, vaccine development, and research is very high. the spike (s) protein, and particularly its receptor-binding domain (rbd), mediates the interaction with the angiotensin-converting enzyme 2 (ace2) receptor on host cells and may be modulated by its structural features. therefore, well-characterized recombinant r ...202133871970
intradermal delivery of a synthetic dna vaccine protects macaques from middle east respiratory syndrome coronavirus.emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), and severe acute respiratory syndrome coronavirus 2 (sars-cov-2), have been associated with human-to-human transmission and significant morbidity and mortality. here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic dna vaccine candidate encoding a full-length mers-cov spike (s) p ...202133886507
sars-cov-2 in animals: potential for unknown reservoir hosts and public health implications.severe acute respiratory syndrome coronavirus 2 (sars-cov-2, previously 2019-ncov) is suspected of having originated in 2019 in china from a coronavirus infected bat of the genus rhinolophus. following the initial emergence, possibly facilitated by a mammalian bridge host, sars-cov-2 is currently transmitted across the globe via efficient human-to-human transmission. results obtained from experimental studies indicate that animal species such as cats, ferrets, raccoon dogs, cynomolgus macaques, ...202133892621
structure and function analysis of a potent human neutralizing antibody ca521fala against sars-cov-2.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is the causative agent of the ongoing covid-19 pandemic, which has resulted in more than two million deaths at 2021 february . there is currently no approved therapeutics for treating covid-19. the sars-cov-2 spike protein is considered a key therapeutic target by many researchers. here we describe the identification of several monoclonal antibodies that target sars-cov-2 spike protein. one human antibody, ca521fala, demonstrated neutr ...202133893388
chicken igy antibodies provide mucosal barrier against sars-cov-2 virus and other pathogens.this mini review includes two case descriptions. it introduces the use of chicken egg yolk antibody (igy) solutions in the prevention and cure of viral and bacterial infections. application for the protection against severe acute respiratory syndrome coronavirus-2 (sars-cov-2), rotavirus, and influenza viruses, as well as for the eradication of pseudomonas aeruginosa, caries, various enteric bacteria and other pathogens, and toxins have been developed. this approach is a fast, reliable, safe, an ...202133899350
susceptibility to sars-cov-2 of cell lines and substrates commonly used to diagnose and isolate influenza and other viruses.co-infection with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and other viruses has been reported. we evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to sars-cov-2. although multiple kidney cell lines from monkeys were susceptible to sars-cov-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. we analyzed mdck cells, which are most commonly used for surveillance and study of ...202133900165
serologic screening of severe acute respiratory syndrome coronavirus 2 infection in cats and dogs during first coronavirus disease wave, the netherlands.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) can infect many animal species, including minks, cats, and dogs. to gain insights into sars-cov-2 infections in cats and dogs, we developed and validated a set of serologic assays, including elisa and virus neutralization. evaluation of samples from animals before they acquired coronavirus disease and samples from cats roaming sars-cov-2-positive mink farms confirmed the suitability of these assays for specific antibody detection. furt ...202133900184
overcoming culture restriction for sars-cov-2 in human cells facilitates the screening of compounds inhibiting viral replication.efforts to mitigate the coronavirus disease 2019 (covid-19) pandemic include the screening of existing antiviral molecules that could be repurposed to treat severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections. although sars-cov-2 replicates and propagates efficiently in african green monkey kidney (vero) cells, antivirals such as nucleos(t)ide analogs (nucs) often show decreased activity in these cells due to inefficient metabolization. sars-cov-2 exhibits low viability in hu ...202133903110
noncanonical crrnas derived from host transcripts enable multiplexable rna detection by cas9.crispr-cas systems recognize foreign genetic material using crispr rnas (crrnas). in type ii systems, a trans-activating crrna (tracrrna) hybridizes to crrnas to drive their processing and utilization by cas9. while analyzing cas9-rna complexes from campylobacter jejuni, we discovered tracrrna hybridizing to cellular rnas, leading to formation of noncanonical crrnas capable of guiding dna targeting by cas9. our discovery inspired the engineering of reprogrammed tracrrnas that link the presence o ...202133906967
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
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
risk factors for covid-19 among healthcare workers. a protocol for a systematic review and meta-analysis.evidence on the spectrum of risk factors for infection with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) among front-line healthcare workers (hcws) has not been well-described. while several studies evaluating the risk factors associated with sars-cov-2 infection among patient-facing and non-patient-facing front-line hcws have been reported since the outbreak of the coronavirus disease in 2019 (covid-19), and several more are still underway. there is, therefore, an immediate need ...202133945546
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
immunomodulatory and antioxidant activity from indonesian anti-degenerative herbs water extract.the spread of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has made the number of patients gradually increase. currently, the vaccine of sars-cov-2 is being researched and most of the people have to trust their immune system and being healthy as long as they could in the mean times. high antioxidant food is recommended for the people whom currently are reducing their activity from home with good exercise. therefore, this research was focused on the indonesian anti-degenerative he ...202133977681
identification of t cell epitopes in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 in rhesus macaques.the t cell response is an important detection index in severe acute respiratory syndrome coronavirus 2 (sars-cov-2) vaccine development. the present study was undertaken to determine the t cell epitopes in the spike (s) protein of sars-cov-2 that dominate the t cell responses in sars-cov-2-infected patients. pbmcs from rhesus macaques vaccinated with a dna vaccine encoding the full-length s protein were isolated, and an elispot assay was used to identify the recognized t cell epitopes among a to ...202133980582
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
northern pig-tailed macaques ( macaca leonina) infected with sars-cov-2 show rapid viral clearance and persistent immune response.coronavirus disease 2019 (covid-19), which is caused by severe acute respiratory syndrome coronavirus (sars-cov-2), has become an unprecedented global health emergency. at present, sars-cov-2-infected nonhuman primates are considered the gold standard animal model for covid-19 research. here, we showed that northern pig-tailed macaques ( macaca leonina, npms) supported sars-cov-2 replication. furthermore, compared with rhesus macaques, npms showed rapid viral clearance in lung tissues, nose swab ...202133998182
fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies.natural antibodies (abs) can target host glycans on the surface of pathogens. we studied the evolution of glycan-reactive b cells of rhesus macaques and humans using glycosylated hiv-1 envelope (env) as a model antigen. 2g12 is a broadly neutralizing ab (bnab) that targets a conserved glycan patch on env of geographically diverse hiv-1 strains using a unique heavy-chain (vh) domain-swapped architecture that results in fragment antigen-binding (fab) dimerization. here, we describe hiv-1 env fab-d ...202134019795
compartmental model suggests importance of innate immune response to covid-19 infection in rhesus macaques.the pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has quickly spread worldwide, creating a serious health crisis. the virus is primarily associated with flu-like symptoms but can also lead to severe pathologies and death. we here present an ordinary differential equation model of the intrahost immune response to sars-cov-2 infection, fitted to experimental data gleaned from rhesus macaques. the model is calibrated to data from a nonlethal infection, but the mo ...202134037874
plant-produced receptor-binding domain of sars-cov-2 elicits potent neutralizing responses in mice and non-human primates.the emergence of coronavirus disease 2019 (covid-19) caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has affected global public health and economy. despite the substantial efforts, only few vaccines are currently approved and some are in the different stages of clinical trials. as the disease rapidly spreads, an affordable and effective vaccine is urgently needed. in this study, we investigated the immunogenicity of plant-produced receptor-binding domain (rbd) of sars-cov- ...202134054909
sars coronavirus outbreaks past and present-a comparative analysis of sars-cov-2 and its predecessors.the coronavirus disease 2019 (covid-19), a pneumonic disease caused by the sars coronavirus 2 (sars-cov-2), is the 7th coronavirus to have successfully infected and caused an outbreak in humans. genome comparisons have shown that previous isolates, the sars-related coronavirus (sarsr-cov), including the sars-cov are closely related, yet different in disease manifestation. several explanations were suggested for the undetermined origin of sars-cov-2, in particular, bats, avian and malayan pangoli ...202134061288
survival of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and herpes simplex virus 1 (hsv-1) on foods stored at refrigerated temperature.outbreaks of coronavirus infectious disease 2019 (covid-19) in meat processing plants and media reports of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) detection on foods have raised concerns of a public health risk from contaminated foods. we used herpes simplex virus 1, a non-biosafety level 3 (non-bsl3) enveloped virus, as a surrogate to develop and validate methods before assessing the survival of infectious sars-cov-2 on foods. several food types, including chicken, seafood, ...202134064494
first description of sars-cov-2 infection in two feral american mink (neovison vison) caught in the wild.severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the causal agent of covid-19, is considered a pathogen of animal origin that is mainly transmitted from human to human. several animal species can be naturally or experimentally infected by sars-cov-2, with compelling evidence that mink is highly susceptible to sars-cov-2 infection. human-to-mink infection cases have been reported and there are also suggestions that mink-to-human infection occurs. mink infections have been reported to ...202134065657
a synthetic peptide ctl vaccine targeting nucleocapsid confers protection from sars-cov-2 challenge in rhesus macaques.persistent transmission of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has given rise to a covid-19 pandemic. several vaccines, conceived in 2020, that evoke protective spike antibody responses are being deployed in mass public health vaccination programs. recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.202134070152
the second wave of sars-cov-2 circulation-antibody detection in the domestic cat population in germany.registered cases of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections in the german human population increased rapidly during the second wave of the sars-cov-2 pandemic in winter 2020/21. since domestic cats are susceptible to sars-cov-2, the occurrence of trans-species transmission needs to be monitored. a previous serosurvey during the first wave of the pandemic detected antibodies against sars-cov-2 in 0.65% of feline serum samples that were randomly sampled across germa ...202134072254
a human antibody of potent efficacy against sars-cov-2 in rhesus macaques showed strong blocking activity to b.1.351.severe acute respiratory syndrome coronavirus-2 (sars-cov-2), which causes coronavirus disease-2019 (covid-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hace2) via its spike 1 protein during infection. after the virus sequence was published, we identified two potent antibodies against the sars-cov-2 receptor binding domain (rbd) from antibody libraries using a phage-to-yeast (pty) display platform in only 10 days. our lead antibody jmb2002, now in a phase 1 clinical ...202134097570
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
endangered mountain gorillas and covid-19: one health lessons for prevention and preparedness during a global pandemic.the world's 1063 mountain gorillas (gorilla beringei beringei) live in two subpopulations at the borders of the democratic republic of congo, rwanda, and uganda. the majority of mountain gorillas are human-habituated to facilitate tourism and research, which brings mountain gorillas into close proximity of people daily. wild great apes are proven to be susceptible to human pathogens, including viruses that have caused fatal respiratory disease in mountain gorillas (e.g., human metapneumovirus1 ) ...202134110030
immunogenic potential of dna vaccine candidate, zycov-d against sars-cov-2 in animal models.severe acute respiratory syndrome coronavirus 2 (sars-cov-2), initially originated in china in year 2019 and spread rapidly across the globe within 5 months, causing over 96 million cases of infection and over 2 million deaths. huge efforts were undertaken to bring the covid-19 vaccines in clinical development, so that it can be made available at the earliest, if found to be efficacious in the trials. we developed a candidate vaccine zycov-d comprising of a dna plasmid vector carrying the gene e ...202134120764
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
binding and molecular basis of the bat coronavirus ratg13 virus to ace2 in humans and other species.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has been spreading worldwide, causing a global pandemic. bat-origin ratg13 is currently the most phylogenetically related virus. here we obtained the complex structure of the ratg13 receptor binding domain (rbd) with human ace2 (hace2) and evaluated binding of ratg13 rbd to 24 additional ace2 orthologs. by substituting residues in the ratg13 rbd with their counterparts in the sars-cov-2 rbd, we found that residue 501, the major positio ...202134139177
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
cell-mimicking nanodecoys neutralize sars-cov-2 and mitigate lung injury in a non-human primate model of covid-19.coronavirus disease 2019 (covid-19), caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. angiotensin-converting enzyme 2 (ace2) plays a fundamental role in sars-cov-2 pathogenesis because it allows viral entry into host cells. here we show that ace2 nanodecoys derived from human lung spheroid cells (lscs) can bind and neutralize sars-cov-2 and protect the host lung cells from inf ...202134140674
sars-cov-2 aerosol exhaled by experimentally infected cynomolgus monkeys.we analyzed size of severe acute respiratory coronavirus 2 (sars-cov-2) aerosol particles shed by experimentally infected cynomolgus monkeys. most exhaled particles were small, and virus was mainly released early during infection. by postinfection day 6, no virus was detected in breath, but air in the isolator contained large quantities of aerosolized virus.202134152969
natural sars-cov-2 infection in kept ferrets, spain.we found severe acute respiratory syndrome coronavirus 2 rna in 6 (8.4%) of 71 ferrets in central spain and isolated and sequenced virus from 1 oral and 1 rectal swab specimen. natural infection occurs in kept ferrets when virus circulation among humans is high. however, small ferret collections probably cannot maintain virus circulation.202134152974
activation of nf-κb and induction of proinflammatory cytokine expressions mediated by orf7a protein of sars-cov-2.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is the causative agent for coronavirus disease 2019 (covid-19) that emerged in human populations recently. severely ill covid-19 patients exhibit the elevation of proinflammatory cytokines, and such an unbalanced production of proinflammatory cytokines is linked to acute respiratory distress syndrome with high mortality in covid-19 patients. our study provides evidence that the orf3a, m, orf7a, and n proteins of sars-cov-2 were nf-κb a ...202134188167
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
pharmacokinetic profiles of a sars-cov-2 neutralizing antibody bd-604 in cynomolgus monkeys.currently, severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has spread worldwide as a severe pandemic and effective therapeutic medications are urgently needed. as reported previously, bd-604 is a fully human monoclonal antibody with strong in vitro and in vivo neutralizing activity to sars-cov-2.202134215019
severe acute respiratory syndrome coronavirus (sars-cov-1) and middle east respiratory syndrome coronavirus (mers-cov) infections in pregnancy - an overview.severe acute respiratory syndrome coronavirus (sars-cov-1) and middle east respiratory syndrome coronavirus (mers-cov) infections, like most other viruses that affect the respiratory tract can cause severe maternal illness and adverse pregnancy outcomes. they are not only highly transmissible (acquired through droplets), but host reservoirs such as dromedary camels for mers-cov and masked palm civet for sars-cov-1 are critical links in the onset of outbreaks. clinically they present with flu-lik ...202134218204
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
in vitro characterization of fitness and convalescent antibody neutralization of sars-cov-2 cluster 5 variant emerging in mink at danish farms.in addition to humans, severe acute respiratory syndrome coronavirus 2 (sars-cov-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. among these, mink are particularly susceptible. indeed, 10 countries in europe and north america reported sars-cov-2 infection among mink on fur farms. in denmark, sars-cov-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions wi ...202134248922
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
inferring the ecological niche of bat viruses closely related to sars-cov-2 using phylogeographic analyses of rhinolophus species.the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is the causal agent of the coronavirus disease 2019 (covid-19) pandemic. to date, viruses closely related to sars-cov-2 have been reported in four bat species: rhinolophus acuminatus, rhinolophus affinis, rhinolophus malayanus, and rhinolophus shameli. here, we analysed 343 sequences of the mitochondrial cytochrome c oxidase subunit 1 gene (co1) from georeferenced bats of the four rhinolophus species identified as reservoirs of vir ...202134253798
identification of a novel lineage bat sars-related coronaviruses that use bat ace2 receptor.severe respiratory disease coronavirus-2 (sars-cov-2) has been the most devastating disease covid-19 in the century. one of the unsolved scientific questions of sars-cov-2 is the animal origin of this virus. bats and pangolins are recognized as the most probable reservoir hosts that harbour highly similar sars-cov-2 related viruses (sarsr-cov-2). this study identified a novel lineage of sarsr-covs, including ratg15 and seven other viruses, from bats at the same location where we found ratg13 in ...202134263709
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
dentistry and the pandemic: a year of reckoning.in march 2020, the world that we know irrevocably changed forever. it feels like groundhog day all over again, and it seems that the nightmare is here to stay. it all began on the january 8, 2020, when china grimly announced that coronavirus disease-2019 (covid-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2)1 but it was not until march 2020 that the situation swiftly careened out of control and is unequivocally posing the greatest challenge to humanity ...202134266997
interferon-armed rbd dimer enhances the immunogenicity of rbd for sterilizing immunity against sars-cov-2.severe acute respiratory syndrome coronavirus 2 (sars-cov-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. a major challenge is that the receptor-binding domain (rbd)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. to enhance antigen processing and cross-presentation in draining lymph nodes (dlns), we developed an interferon (ifn)-armed rbd dimerized by an i ...202134267349
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
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
treatment with dry hydrogen peroxide accelerates the decay of severe acute syndrome coronavirus-2 on non-porous hard surfaces.disinfection of contaminated or potentially contaminated surfaces has become an integral part of the mitigation strategies for controlling coronavirus disease 2019. whilst a broad range of disinfectants are effective in inactivating severe acute respiratory syndrome coronavirus-2 (sars-cov-2), application of disinfectants has a low throughput in areas that receive treatments. disinfection of large surface areas often involves the use of reactive microbiocidal materials, including ultraviolet ger ...202134273464
a recombinant spike protein subunit vaccine confers protective immunity against sars-cov-2 infection and transmission in hamsters.multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) are necessary to respond to the ongoing coronavirus disease 2019 (covid-19) pandemic. here, we developed a protein subunit vaccine composed of spike ectodomain protein (strifk) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (fh002c). strifk-fh002c generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus ...202134285130
peridomestic mammal susceptibility to severe acute respiratory syndrome coronavirus 2 infection.wild animals have been implicated as the origin of severe acute respiratory syndrome coronavirus 2 (sars-cov-2), but it is largely unknown how the virus affects most wildlife species and if wildlife could ultimately serve as a reservoir for maintaining the virus outside the human population. we show that several common peridomestic species, including deer mice, bushy-tailed woodrats, and striped skunks, are susceptible to infection and can shed the virus in respiratory secretions. in contrast, w ...202134286685
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
host- and species-dependent quasispecies divergence of severe acute respiratory syndrome coronavirus-2 in non-human primate models.recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) have been continuously reported worldwide. however, the precise evaluation of sars-cov-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. in this report, we performed deep sequencing for seed virus and sars-cov-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucl ...202134305860
recovery from acute sars-cov-2 infection and development of anamnestic immune responses in t cell-depleted rhesus macaques.severe coronavirus disease 2019 (covid-19) has been associated with t cell lymphopenia, but no causal effect of t cell deficiency on disease severity has been established. to investigate the specific role of t cells in recovery from severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infections, we studied rhesus macaques that were depleted of either cd4+, cd8+, or both t cell subsets prior to infection. peak virus loads were similar in all groups, but the resolution of virus in the t c ...202134311582
intranasal chadox1 ncov-19/azd1222 vaccination reduces viral shedding after sars-cov-2 d614g challenge in preclinical models.chadox1 ncov-19/azd1222 is an approved adenovirus-based vaccine for severe acute respiratory syndrome coronavirus 2 (sars-cov-2) currently being deployed globally. previous studies in rhesus macaques revealed that intramuscular vaccination with chadox1 ncov-19/azd1222 provided protection against pneumonia but did not reduce shedding of sars-cov-2 from the upper respiratory tract. here, we investigated whether intranasally administered chadox1 ncov-19 reduces detection of virus in nasal swabs aft ...202134315826
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
viral metagenomics reveals diverse viruses in the feces samples of raccoon dogs.raccoon dogs as an ancient species of canidae are the host of many viruses, including rabies virus, canine distemper virus, severe acute respiratory syndrome coronavirus, and so on. with the development of raccoon dog breeding in recent years, some viruses which infected poultry or pigs were also detected from raccoon dogs. at present, the fecal virome of raccoon dogs has been rarely studied. using an unbiased viral metagenomic approach, we investigated the fecal virome in raccoon dogs collected ...202134322538
sars-cov-2 in animals: from potential hosts to animal models.within only one year after the first detection of severe acute respiratory syndrome coronavirus-2 (sars-cov-2), nearly 100 million infections were reported in the human population globally, with more than two million fatal cases. while sars-cov-2 most likely originated from a natural wildlife reservoir, neither the immediate viral precursor nor the reservoir or intermediate hosts have been identified conclusively. due to its zoonotic origin, sars-cov-2 may also be relevant to animals. thus, to e ...202134353482
resveratrol and pterostilbene inhibit sars-cov-2 replication in air-liquid interface cultured human primary bronchial epithelial cells.the current covid-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and has an enormous impact on human health and economy. in search for therapeutic options, researchers have proposed resveratrol, a food supplement with known antiviral, anti-inflammatory, and antioxidant properties as an advantageous antiviral therapy for sars-cov-2 infection. here, we provide evidence that both resveratrol and its metabolically more stable structural analog, pterostilbene, e ...202134372541
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
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