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1.
Vet Q ; 42(1): 125-147, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35584308

RESUMO

Swine coronaviruses (SCoVs) are one of the most devastating pathogens affecting the livelihoods of farmers and swine industry across the world. These include transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine respiratory coronavirus (PRCV), porcine hemagglutinating encephalomyelitis virus (PHEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and porcine delta coronavirus (PDCoV). Coronaviruses infect a wide variety of animal species and humans because these are having single stranded-RNA that accounts for high mutation rates and thus could break the species barrier. The gastrointestinal, cardiovascular, and nervous systems are the primary organ systems affected by SCoVs. Infection is very common in piglets compared to adult swine causing high mortality in the former. Bat is implicated to be the origin of all CoVs affecting animals and humans. Since pig is the only domestic animal in which CoVs cause a wide range of diseases; new coronaviruses with high zoonotic potential could likely emerge in the future as observed in the past. The recently emerged severe acute respiratory syndrome coronavirus virus-2 (SARS-CoV-2), causing COVID-19 pandemic in humans, has been implicated to have animal origin, also reported from few animal species, though its zoonotic concerns are still under investigation. This review discusses SCoVs and their epidemiology, virology, evolution, pathology, wildlife reservoirs, interspecies transmission, spill-over events and highlighting their emerging threats to swine population. The role of pigs amid ongoing SARS-CoV-2 pandemic will also be discussed. A thorough investigation should be conducted to rule out zoonotic potential of SCoVs and to design appropriate strategies for their prevention and control.


Assuntos
COVID-19 , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Alphacoronavirus , Animais , COVID-19/epidemiologia , COVID-19/veterinária , Humanos , Pandemias , SARS-CoV-2 , Suínos , Doenças dos Suínos/epidemiologia
2.
Viruses ; 14(4)2022 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-35458562

RESUMO

Porcine enteric coronaviruses have caused immense economic losses to the global pig industry, and pose a potential risk for cross-species transmission. The clinical symptoms of the porcine enteric coronaviruses (CoVs) are similar, making it difficult to distinguish between the specific pathogens by symptoms alone. Here, a multiplex nucleic acid detection platform based on CRISPR/Cas12a and multiplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) was developed for the detection of four diarrhea CoVs: porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). With this strategy, we realized a visual colorimetric readout visible to the naked eye without specialized instrumentation by using a ROX-labeled single-stranded DNA-fluorescence-quenched (ssDNA-FQ) reporter. Our method achieved single-copy sensitivity with no cross-reactivity in the identification and detection of the target viruses. In addition, we successfully detected these four enteric CoVs from RNA of clinical samples. Thus, we established a rapid, sensitive, and on-site multiplex molecular differential diagnosis technology for porcine enteric CoVs.


Assuntos
Infecções por Coronavirus , Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Alphacoronavirus , Animais , Sistemas CRISPR-Cas , Coronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/genética , Infecções por Coronavirus/veterinária , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Vírus da Diarreia Epidêmica Suína/genética , DNA Polimerase Dirigida por RNA/genética , Sensibilidade e Especificidade , Suínos
3.
Int J Mol Sci ; 23(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35409315

RESUMO

Swine enteric coronavirus (SeCoV) causes acute gastroenteritis and high mortality in newborn piglets. Since the last century, porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) have swept farms all over the world and caused substantial economic losses. In recent years, porcine delta coronavirus (PDCoV) and swine acute diarrhea syndrome coronavirus (SADS-CoV) have been emerging SeCoVs. Some of them even spread across species, which made the epidemic situation of SeCoV more complex and changeable. Recent studies have begun to reveal the complex SeCoV-host interaction mechanism in detail. This review summarizes the current advances in autophagy, apoptosis, and innate immunity induced by SeCoV infection. These complex interactions may be directly involved in viral replication or the alteration of some signal pathways.


Assuntos
Infecções por Coronavirus , Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Alphacoronavirus , Animais , Interações Hospedeiro-Patógeno , Suínos
4.
Viruses ; 14(4)2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35458511

RESUMO

BACKGROUND: Studies have linked bats to outbreaks of viral diseases in human populations such as SARS-CoV-1 and MERS-CoV and the ongoing SARS-CoV-2 pandemic. METHODS: We carried out a longitudinal survey from August 2020 to July 2021 at two sites in Zimbabwe with bat-human interactions: Magweto cave and Chirundu farm. A total of 1732 and 1866 individual bat fecal samples were collected, respectively. Coronaviruses and bat species were amplified using PCR systems. RESULTS: Analysis of the coronavirus sequences revealed a high genetic diversity, and we identified different sub-viral groups in the Alphacoronavirus and Betacoronavirus genus. The established sub-viral groups fell within the described Alphacoronavirus sub-genera: Decacovirus, Duvinacovirus, Rhinacovirus, Setracovirus and Minunacovirus and for Betacoronavirus sub-genera: Sarbecoviruses, Merbecovirus and Hibecovirus. Our results showed an overall proportion for CoV positive PCR tests of 23.7% at Chirundu site and 16.5% and 38.9% at Magweto site for insectivorous bats and Macronycteris gigas, respectively. CONCLUSIONS: The higher risk of bat coronavirus exposure for humans was found in December to March in relation to higher viral shedding peaks of coronaviruses in the parturition, lactation and weaning months of the bat populations at both sites. We also highlight the need to further document viral infectious risk in human/domestic animal populations surrounding bat habitats in Zimbabwe.


Assuntos
Alphacoronavirus , COVID-19 , Quirópteros , Animais , COVID-19/epidemiologia , Evolução Molecular , Feminino , Genoma Viral , Filogenia , SARS-CoV-2/genética , Zimbábue/epidemiologia
5.
Proc Natl Acad Sci U S A ; 119(18): e2118126119, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35476513

RESUMO

Zoonotic transmission of coronaviruses poses an ongoing threat to human populations. Endemic outbreaks of swine acute diarrhea syndrome coronavirus (SADS-CoV) have caused severe economic losses in the pig industry and have the potential to cause human outbreaks. Currently, there are no vaccines or specific antivirals against SADS-CoV, and our limited understanding of SADS-CoV host entry factors could hinder prompt responses to a potential human outbreak. Using a genomewide CRISPR knockout screen, we identified placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection. Knockout of PLAC8 abolished SADS-CoV infection, which was restored by complementing PLAC8 from multiple species, including human, rhesus macaques, mouse, pig, pangolin, and bat, suggesting a conserved infection pathway and susceptibility of SADS-CoV among mammals. Mechanistically, PLAC8 knockout does not affect viral entry; rather, knockout cells displayed a delay and reduction in viral subgenomic RNA expression. In a swine primary intestinal epithelial culture (IEC) infection model, differentiated cultures have high levels of PLAC8 expression and support SADS-CoV replication. In contrast, expanding IECs have low levels of PLAC8 expression and are resistant to SADS-CoV infection. PLAC8 expression patterns translate in vivo; the immunohistochemistry of swine ileal tissue revealed high levels of PLAC8 protein in neonatal compared to adult tissue, mirroring the known SADS-CoV pathogenesis in neonatal piglets. Overall, PLAC8 is an essential factor for SADS-CoV infection and may serve as a promising target for antiviral development for potential pandemic SADS-CoV.


Assuntos
Alphacoronavirus , Infecções por Coronavirus , Doenças dos Suínos , Alphacoronavirus/genética , Animais , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Infecções por Coronavirus/epidemiologia , Suínos
6.
Viruses ; 14(3)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35336963

RESUMO

The ongoing COVID-19 pandemic has stimulated a search for reservoirs and species potentially involved in back and forth transmission. Studies have postulated bats as one of the key reservoirs of coronaviruses (CoVs), and different CoVs have been detected in bats. So far, CoVs have not been found in bats in Sweden and we therefore tested whether they carry CoVs. In summer 2020, we sampled a total of 77 adult bats comprising 74 Myotis daubentonii, 2 Pipistrellus pygmaeus, and 1 M. mystacinus bats in southern Sweden. Blood, saliva and feces were sampled, processed and subjected to a virus next-generation sequencing target enrichment protocol. An Alphacoronavirus was detected and sequenced from feces of a M. daubentonii adult female bat. Phylogenetic analysis of the almost complete virus genome revealed a close relationship with Finnish and Danish strains. This was the first finding of a CoV in bats in Sweden, and bats may play a role in the transmission cycle of CoVs in Sweden. Focused and targeted surveillance of CoVs in bats is warranted, with consideration of potential conflicts between public health and nature conservation required as many bat species in Europe are threatened and protected.


Assuntos
Alphacoronavirus , COVID-19 , Quirópteros , Animais , COVID-19/epidemiologia , Feminino , Humanos , Pandemias , Filogenia , Suécia
7.
Virus Res ; 313: 198742, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35283248

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an emerging swine enteric coronavirus that causes vomiting, severe diarrhea, dehydration and death in suckling piglets. NS7a is putative accessory protein that is predicted to be encoded by SADS-CoV, but still to be confirmed experimentally. In the present study, recombinant NS7a protein was expressed in a prokaryotic expression system and used as an antigen to prepare monoclonal antibodies (mAbs) specific to NS7a protein. We obtained two anti-NS7a mAbs, termed AH5 and EH3, that were shown by western blotting to react with the natural NS7a protein in Vero E6 cells infected with SADS-CoV. Using the produced mAbs, we observed by confocal microscopy that NS7a protein was expressed in the cytoplasm. Further studies revealed that the motif 31VNTWQEFA38 was the minimal unit of the linear B-cell epitope recognized by mAb AH5, and the motif 82FDLFERF88 was the minimal unit of the linear B-cell epitope recognized by mAb EH3. Alignment of amino acids showed that these two epitopes were highly conserved among different SADS-CoV strains and SADS-related coronaviruses from bats, but with one substitution in these two motifs in bat coronavirus HKU2. In summary, we generated and characterized two mAbs against SADS-CoV NS7a protein, and demonstrated NS7a expression in SADS-CoV-infected cells for the first time.


Assuntos
Alphacoronavirus , Coronavirus , Alphacoronavirus/genética , Animais , Anticorpos Monoclonais , Mapeamento de Epitopos , Suínos
8.
Viruses ; 14(2)2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35215796

RESUMO

Bats are widespread mammals of the order Chiroptera. They are key for ecosystem functioning, participating in crucial processes. Their unique ability amongst mammals to fly long distances, their frequently large population sizes, and their longevity favor infectious agent persistence and spread. This includes a large variety of viruses, encompassing many important zoonotic ones that cause severe diseases in humans and domestic animals. Despite this, the understanding of the viral ecological diversity residing in bat populations remains unclear, which complicates the determination of the origins of zoonotic viruses. To gain knowledge on the viral community of a widely distributed insectivorous bat species, we characterized the guano virome of a native Chilean bat species (Myotis chiloensis (Waterhouse, 1840)). By applying a novel enrichment strategy, we were able to secure a consequent percentage of viral reads, providing unprecedented resolution for a bat virome. This in turn enabled us to identify and assemble a new bat alphacoronavirus from Chilean bats closely related to PEDV, an important viral pathogen with high mortality rates in suckling piglets. This study highlights the importance of applying and improving high-resolution virome studies in this vital order to ultimately enhance epidemiological surveillance for potentially zoonotic pathogens.


Assuntos
Alphacoronavirus/genética , Quirópteros/virologia , Genoma Viral/genética , Viroma , Alphacoronavirus/classificação , Alphacoronavirus/isolamento & purificação , Animais , Chile , Fezes/virologia , Filogenia , RNA Viral/genética , Viroma/genética
9.
Viruses ; 14(2)2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35215931

RESUMO

Coronaviruses (CoV) are divided into the genera α-CoVs, ß-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and ß-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the ß-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and ß-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and ß-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus.


Assuntos
Alphacoronavirus/genética , Alphacoronavirus/isolamento & purificação , Quirópteros/virologia , Infecções por Coronavirus/veterinária , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Genoma Viral , Alphacoronavirus/classificação , Animais , Cavernas/virologia , Infecções por Coronavirus/virologia , Evolução Molecular , Feminino , Masculino , Filogenia , Análise de Sequência de DNA , Sri Lanka
10.
Emerg Microbes Infect ; 11(1): 699-702, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35156544

RESUMO

Here we review the existing evidence of animal alphacoronaviruses (Alphacoronavirus 1 species) circulating in human patients with acute respiratory illness. Thus far, the viruses similar to canine, feline and porcine alphacoronaviruses (including the most recent CCoV-HuPn-2018 and HuCCoV_Z19) have been detected in humans in Haiti, Malaysia, Thailand, and USA. The available data suggest that these viruses emerged in different geographic locations independently and have circulated in humans for at least 20 years. Additional studies are needed to investigate their prevalence and disease impact.


Assuntos
Alphacoronavirus , Infecções por Coronavirus , Animais , Gatos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Cães , Humanos , Malásia , Filogenia , Sistema Respiratório , Suínos , Tailândia
11.
Viruses ; 14(2)2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-35215778

RESUMO

Bats are a reservoir for coronaviruses (CoVs) that periodically spill over to humans, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. A collection of 174 bat samples originating from South Dakota, Minnesota, Iowa, and Nebraska submitted for rabies virus testing due to human exposure were analyzed using a pan-coronavirus PCR. A previously partially characterized CoV, Eptesicus bat CoV, was identified in 12 (6.9%) samples by nested RT-PCR. Six near-complete genomes were determined. Genetic analysis found a high similarity between all CoV-positive samples, Rocky Mountain bat CoV 65 and alphacoronavirus HCQD-2020 recently identified in South Korea. Phylogenetic analysis of genome sequences showed EbCoV is closely related to bat CoV HKU2 and swine acute diarrhea syndrome CoV; however, topological incongruences were noted for the spike gene that was more closely related to porcine epidemic diarrhea virus. Similar to some alphaCoVs, a novel gene, ORF7, was discovered downstream of the nucleocapsid, whose protein lacked similarity to known proteins. The widespread circulation of EbCoV with similarities to bat viruses that have spilled over to swine warrants further surveillance.


Assuntos
Alphacoronavirus/classificação , Alphacoronavirus/genética , Quirópteros/virologia , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Filogenia , Alphacoronavirus/isolamento & purificação , Animais , Genoma Viral , Iowa , Meio-Oeste dos Estados Unidos , Minnesota , República da Coreia , Análise de Sequência de DNA , South Dakota , Zoonoses Virais/transmissão
12.
J Med Virol ; 94(7): 3251-3256, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35211991

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered bat-origin coronavirus with fatal pathogenicity for neonatal piglets. There is no vaccine to prevent SADS-CoV infection or clinically approved drugs targeting SADS-CoV. Therefore, unraveling cellular factors that regulate SADS-CoV for cell entry is critical to understanding the viral transmission mechanism and provides a potential therapeutic target for SADS-CoV cure. Here, we showed that Type I interferon (IFN-I) pretreatment potently blocks SADS-CoV entry into cells using lentiviral pseudo-virions as targets whose entry is driven by the SADS-CoV Spike glycoprotein. IFN-I-mediated inhibition of SADS-CoV entry and replication was dramatically impaired in the absence of TET2. These results suggest TET2 is found to serve as a checkpoint of IFN-I-meditated inhibition on the cell entry of SADS-CoV, and our discovery might constitute a novel treatment option to combat against SADS-CoV.


Assuntos
Alphacoronavirus , Quirópteros , Dioxigenases , Alphacoronavirus/fisiologia , Animais , Proteínas de Ligação a DNA/fisiologia , Dioxigenases/fisiologia , Humanos , Interferon Tipo I , Glicoproteína da Espícula de Coronavírus
13.
Virology ; 565: 96-105, 2022 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-34768113

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered enteric coronavirus. We have previously shown that the caspase-dependent FASL-mediated and mitochondrion-mediated apoptotic pathways play a central role in SADS-CoV-induced apoptosis, which facilitates viral replication. However, the roles of intracellular signaling pathways in SADS-CoV-mediated cell apoptosis and the relative advantages that such pathways confer on the host or virus remain largely unknown. In this study, we show that SADS-CoV induces the activation of ERK during infection, irrespective of viral biosynthesis. The knockdown or chemical inhibition of ERK1/2 significantly suppressed viral protein expression and viral progeny production. The inhibition of ERK activation also circumvented SADS-CoV-induced apoptosis. Taken together, these data suggest that ERK activation is important for SADS-CoV replication, and contributes to the virus-mediated changes in host cells. Our findings demonstrate the takeover of a particular host signaling mechanism by SADS-CoV and identify a potential approach to inhibiting viral spread.


Assuntos
Alphacoronavirus/fisiologia , Sistema de Sinalização das MAP Quinases , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Replicação Viral , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/metabolismo , Chlorocebus aethiops , Técnicas de Silenciamento de Genes , Interações Hospedeiro-Patógeno , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Inibidores de Proteínas Quinases/farmacologia , Suínos , Células Vero , Replicação Viral/efeitos dos fármacos
14.
J Med Virol ; 94(1): 186-196, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34427932

RESUMO

In classical viral infections, the avidity of immunoglobulin G (IgG) is low during acute infection and high a few months later. As recently reported, SARS-CoV-2 infections are not following this scheme, but they are rather characterized by incomplete avidity maturation. This study was performed to clarify whether infection with seasonal coronaviruses also leads to incomplete avidity maturation. The avidity of IgG toward the nucleoprotein (NP) of the seasonal coronaviruses 229E, NL63, OC43, HKU1 and of SARS-CoV-2 was determined in the sera from 88 healthy, SARS-CoV-2-negative subjects and in the sera from 70 COVID-19 outpatients, using the recomLine SARS-CoV-2 assay with recombinant antigens. In the sera from SARS-CoV-2-negative subjects, incomplete avidity maturation (persistent low and intermediate avidity indices) was the lowest for infections with the alpha-coronaviruses 229E (33.3%) and NL63 (61.3%), and the highest for the beta-coronaviruses OC43 (77.5%) and HKU1 (71.4%). In the sera from COVID-19 patients, the degree of incomplete avidity maturation of IgG toward NP of 223E, OC43, and HKU1 was not significantly different from that found in SARS-CoV-2-negative subjects, but a significant increase in avidity was observed for IgG toward NP of NL63. Though there was no cross-reaction between SARS-CoV-2 and seasonal coronaviruses, higher concentrations of IgG directed toward seasonal coronaviruses seemed to indirectly increase avidity maturation of IgG directed toward SARS-CoV-2. Our data show that incomplete IgG avidity maturation represents a characteristic consequence of coronavirus infections. This raises problems for the serological differentiation between acute and past infections and may be important for the biology of coronaviruses.


Assuntos
Alphacoronavirus/imunologia , Afinidade de Anticorpos , Betacoronavirus/imunologia , COVID-19/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Coronavirus Humano NL63/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Coronavirus Humano OC43/imunologia , Reações Cruzadas , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Estações do Ano , Adulto Jovem
15.
Sci Rep ; 11(1): 24145, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921180

RESUMO

Recent studies suggest that coronaviruses circulate widely in Southeast Asian bat species and that the progenitors of the SARS-Cov-2 virus could have originated in rhinolophid bats in the region. Our objective was to assess the diversity and circulation patterns of coronavirus in several bat species in Southeast Asia. We undertook monthly live-capture sessions and sampling in Cambodia over 17 months to cover all phases of the annual reproduction cycle of bats and test specifically the association between their age and CoV infection status. We additionally examined current information on the reproductive phenology of Rhinolophus and other bat species presently known to occur in mainland southeast China, Vietnam, Laos and Cambodia. Results from our longitudinal monitoring (573 bats belonging to 8 species) showed an overall proportion of positive PCR tests for CoV of 4.2% (24/573) in cave-dwelling bats from Kampot and 4.75% (22/463) in flying-foxes from Kandal. Phylogenetic analysis showed that the PCR amplicon sequences of CoVs (n = 46) obtained clustered in Alphacoronavirus and Betacoronavirus. Interestingly, Hipposideros larvatus sensu lato harbored viruses from both genera. Our results suggest an association between positive detections of coronaviruses and juvenile and immature bats in Cambodia (OR = 3.24 [1.46-7.76], p = 0.005). Since the limited data presently available from literature review indicates that reproduction is largely synchronized among rhinolophid and hipposiderid bats in our study region, particularly in its more seasonal portions (above 16° N), this may lead to seasonal patterns in CoV circulation. Overall, our study suggests that surveillance of CoV in insectivorous bat species in Southeast Asia, including SARS-CoV-related coronaviruses in rhinolophid bats, could be targeted from June to October for species exhibiting high proportions of juveniles and immatures during these months. It also highlights the need to develop long-term longitudinal surveys of bats and improve our understanding of their ecology in the region, for both biodiversity conservation and public health reasons.


Assuntos
Alphacoronavirus/genética , Betacoronavirus/genética , COVID-19/transmissão , Quirópteros/crescimento & desenvolvimento , SARS-CoV-2/genética , Alphacoronavirus/classificação , Animais , Ásia Sudeste/epidemiologia , Betacoronavirus/classificação , COVID-19/epidemiologia , COVID-19/virologia , Camboja/epidemiologia , Quirópteros/classificação , Quirópteros/virologia , Epidemias/prevenção & controle , Evolução Molecular , Genoma Viral/genética , Geografia , Humanos , Estudos Longitudinais , Masculino , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/fisiologia , Especificidade da Espécie
16.
Int J Mol Sci ; 22(22)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34830015

RESUMO

Coronaviruses cause diseases in humans and livestock. The SARS-CoV-2 is infecting millions of human beings, with high morbidity and mortality worldwide. The main protease (Mpro) of coronavirus plays a pivotal role in viral replication and transcription, which, in theory, is an attractive drug target for antiviral drug development. It has been extensively discussed whether Xanthohumol is able to help COVID-19 patients. Here, we report that Xanthohumol, a small molecule in clinical trials from hops (Humulus lupulus), was a potent pan-inhibitor for various coronaviruses by targeting Mpro, for example, betacoronavirus SARS-CoV-2 (IC50 value of 1.53 µM), and alphacoronavirus PEDV (IC50 value of 7.51 µM). Xanthohumol inhibited Mpro activities in the enzymatical assays, while pretreatment with Xanthohumol restricted the SARS-CoV-2 and PEDV replication in Vero-E6 cells. Therefore, Xanthohumol is a potent pan-inhibitor of coronaviruses and an excellent lead compound for further drug development.


Assuntos
Proteases Virais 3C/antagonistas & inibidores , Flavonoides/química , Propiofenonas/química , Inibidores de Proteases/química , SARS-CoV-2/enzimologia , Proteases Virais 3C/química , Proteases Virais 3C/metabolismo , Alphacoronavirus/enzimologia , Alphacoronavirus/fisiologia , Sequência de Aminoácidos , Animais , Sítios de Ligação , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Domínio Catalítico , Chlorocebus aethiops , Coronavirus/enzimologia , Coronavirus/fisiologia , Flavonoides/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Propiofenonas/metabolismo , Propiofenonas/farmacologia , Propiofenonas/uso terapêutico , Inibidores de Proteases/metabolismo , Inibidores de Proteases/farmacologia , Inibidores de Proteases/uso terapêutico , SARS-CoV-2/isolamento & purificação , Alinhamento de Sequência , Células Vero , Replicação Viral/efeitos dos fármacos
17.
Viruses ; 13(11)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34834994

RESUMO

In the last two decades, several coronavirus (CoV) interspecies jumping events have occurred between bats and other animals/humans, leading to major epidemics/pandemics and high fatalities. The SARS epidemic in 2002/2003 had a ~10% fatality. The discovery of SARS-related CoVs in horseshoe bats and civets and genomic studies have confirmed bat-to-civet-to-human transmission. The MERS epidemic that emerged in 2012 had a ~35% mortality, with dromedaries as the reservoir. Although CoVs with the same genome organization (e.g., Tylonycteris BatCoV HKU4 and Pipistrellus BatCoV HKU5) were also detected in bats, there is still a phylogenetic gap between these bat CoVs and MERS-CoV. In 2016, 10 years after the discovery of Rhinolophus BatCoV HKU2 in Chinese horseshoe bats, fatal swine disease outbreaks caused by this virus were reported in southern China. In late 2019, an outbreak of pneumonia emerged in Wuhan, China, and rapidly spread globally, leading to >4,000,000 fatalities so far. Although the genome of SARS-CoV-2 is highly similar to that of SARS-CoV, patient zero and the original source of the pandemic are still unknown. To protect humans from future public health threats, measures should be taken to monitor and reduce the chance of interspecies jumping events, either occurring naturally or through recombineering experiments.


Assuntos
COVID-19/virologia , Quirópteros/virologia , Infecções por Coronavirus/virologia , Coronavirus/fisiologia , Adaptação ao Hospedeiro , Síndrome Respiratória Aguda Grave/virologia , Alphacoronavirus/genética , Alphacoronavirus/fisiologia , Animais , COVID-19/transmissão , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Especificidade de Hospedeiro , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Vírus da SARS/genética , Vírus da SARS/fisiologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/transmissão , Síndrome Respiratória Aguda Grave/veterinária
18.
Viruses ; 13(11)2021 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-34835131

RESUMO

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , SARS-CoV-2/imunologia , Distribuição por Idade , Alphacoronavirus/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Doadores de Sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteção Cruzada , Reações Cruzadas , Epitopos , Feminino , Humanos , Masculino , Fosfoproteínas/imunologia , Serra Leoa , Estados Unidos
19.
Biosci Rep ; 41(12)2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34796903

RESUMO

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and ß-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Endotoxinas/farmacologia , Fragmentos de Peptídeos/farmacologia , Glicoproteína da Espícula de Coronavírus/farmacologia , Alphacoronavirus , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Antígenos CD13/metabolismo , Células CHO , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Cricetulus , Endotoxinas/toxicidade , Hemólise/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/toxicidade , Conformação Proteica em alfa-Hélice , Carneiro Doméstico , Glicoproteína da Espícula de Coronavírus/toxicidade , Relação Estrutura-Atividade
20.
Viruses ; 13(10)2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34696392

RESUMO

Bats have been identified as natural reservoirs of a variety of coronaviruses. They harbor at least 19 of the 33 defined species of alpha- and betacoronaviruses. Previously, the bat coronavirus HKU10 was found in two bat species of different suborders, Rousettus leschenaultia and Hipposideros pomona, in south China. However, its geographic distribution and evolution history are not fully investigated. Here, we screened this viral species by a nested reverse transcriptase PCR in our archived samples collected over 10 years from 25 provinces of China and one province of Laos. From 8004 bat fecal samples, 26 were found to be positive for bat coronavirus HKU10 (BtCoV HKU10). New habitats of BtCoV HKU10 were found in the Yunnan, Guangxi, and Hainan Provinces of China, and Louang Namtha Province in Laos. In addition to H. pomona, BtCoV HKU10 variants were found circulating in Aselliscus stoliczkanus and Hipposideros larvatus. We sequenced full-length genomes of 17 newly discovered BtCoV HKU10 strains and compared them with previously published sequences. Our results revealed a much higher genetic diversity of BtCoV HKU10, particularly in spike genes and accessory genes. Besides the two previously reported lineages, we found six novel lineages in their new habitats, three of which were located in Yunnan province. The genotypes of these viruses are closely related to sampling locations based on polyproteins, and correlated to bat species based on spike genes. Combining phylogenetic analysis, selective pressure, and molecular-clock calculation, we demonstrated that Yunnan bats harbor a gene pool of BtCoV HKU10, with H. pomona as a natural reservoir. The cell tropism test using spike-pseudotyped lentivirus system showed that BtCoV HKU10 could enter cells from human and bat, suggesting a potential interspecies spillover. Continuous studies on these bat coronaviruses will expand our understanding of the evolution and genetic diversity of coronaviruses, and provide a prewarning of potential zoonotic diseases from bats.


Assuntos
Alphacoronavirus/genética , Quirópteros/virologia , Alphacoronavirus/patogenicidade , Animais , Sequência de Bases/genética , Evolução Biológica , China , Quirópteros/genética , Coronavirus/genética , Coronavirus/patogenicidade , Infecções por Coronavirus/virologia , Evolução Molecular , Variação Genética/genética , Genoma Viral/genética , Genótipo , Filogenia , Análise de Sequência de DNA/métodos , Proteínas Virais/genética
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