Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-convertin...Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).展开更多
Streptococcus equi subsp.zooepidemicus(SEZ)is an important zoonotic agent.Here,a virulence-attenuated strain M35246 derived from natural variation of wild-type SEZ ATCC35246 was found.M35246 showed a deletion of 25con...Streptococcus equi subsp.zooepidemicus(SEZ)is an important zoonotic agent.Here,a virulence-attenuated strain M35246 derived from natural variation of wild-type SEZ ATCC35246 was found.M35246 showed a deletion of 25contiguous genes as well as a loss-of-function mutation in covS.Subsequently,a 25-gene-deleted strain(ΔPI),a covS-mutant strain(Mcov S),and relevant complementary strains were constructed and investigated.M35246 and Mcov S were significantly less encapsulated and exhibited poorer anti-phagocytic capacity compared to wild-type SEZ.McovS was significantly more sensitive toβ-lactams,aminoglycosides,macrolides,and lincosamides than wild-type SEZ.M35246,McovS,andΔPI exhibited an increase in median lethal dose(LD_(50))in mice by 10~5,10~5,and 5 times when compared to wild-type SEZ,respectively.Neither M35246 nor McovS were isolated from mice 48 h after being challenged with approximately 2000 times the LD_(50)of wild-type SEZ.Transcriptome analysis showed that 668 significantly differentially expressed genes existed between McovS and wild-type SEZ.Numerous virulence factor-encoding genes and anabolicrelated genes in McovS that were involved in anti-phagocytosis,capsule formation,pathogenicity,and antibiotic resistance were downregulated significantly relative to the wild-type strain.This study revealed that the CovS plays a vital role in the establishment of SEZ virulence.展开更多
In Streptococcus pyogenes, we have described the two-component signal transduction sensor and regulatory systems, CovR/S affect the antimicrobial susceptibility including penicillin G before. But the mechanism how two...In Streptococcus pyogenes, we have described the two-component signal transduction sensor and regulatory systems, CovR/S affect the antimicrobial susceptibility including penicillin G before. But the mechanism how two-component sensor protein CovS modulates penicillin G susceptibility has not been elucidated till date. This study aimed to determine how the CovS affected penicillin G susceptibility in Streptococcus pyogenes by northern blot analysis. At first, we investigated the covS mRNA expression under penicillin G induction. We found that the decrease of covS mRNA expression under Penicillin G stimulation. Next we investigated the expression of cell wall synthesis gene, pbp2a and glmM with use of covS knockout mutants from emm1 Streptococcus pyogenes strain 1529. We found that the cell-wall synthesis gene expression of the ?covS mutant strain were lower than that of the wild-type strain. Furthermore the expression of glmM mRNA gene was lower than the expression of pbp2a mRNA gene in the ?covS mutant strain. The covS-complemented strain almost restored the mRNA expression compared to covS mutant strain. The two-component sensor protein CovS affects the susceptibility to penicillin G in Streptococcus pyogenes by modulation of cell-wall synthesis.展开更多
Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic g...Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.展开更多
Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV...Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.展开更多
Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met th...Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.展开更多
Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompr...Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).展开更多
目的筛选SARS病毒S蛋白的B细胞表位。方法使用SARS-CoV S DNA疫苗免疫BALB/c小鼠,获得SARS病毒S蛋白的免疫血清。人工合成包含169条部分氨基酸序列重叠的SARS-CoV S蛋白的多肽库。将多肽片段包被ELISA板,利用免疫小鼠血清,通过抗体结合...目的筛选SARS病毒S蛋白的B细胞表位。方法使用SARS-CoV S DNA疫苗免疫BALB/c小鼠,获得SARS病毒S蛋白的免疫血清。人工合成包含169条部分氨基酸序列重叠的SARS-CoV S蛋白的多肽库。将多肽片段包被ELISA板,利用免疫小鼠血清,通过抗体结合试验来筛选SARS病毒S蛋白的线性B细胞表位。并将筛选结果与使用B细胞表位分析软件预测的结果进行比较。结果使用重叠肽合成法筛选到SARS-CoV蛋白两条多肽片段S335-352和S442-458,能与免疫动物血清特异性结合,与使用Bcipep数据库预测B细胞表位的结果相一致。结论鉴定了两个新的SARS病毒S蛋白B细胞表位。展开更多
文摘Dear Editor,Historically,dipeptidyl peptidase 4(DPP4),found in alveolar regions,has been recognized as the primary receptor for several merbecoviruses like MERS-CoV(Meyerholz et al.,2016).However,angiotensin-converting enzyme 2(ACE2),highly expressed in the motile cilia of human airway epithelial cells(Sungnak et al.,2020),has been identified as the functional receptor for sarbecoviruses(e.g.,SARS-CoV-2,SARS-CoV)and setracoviruses(e.g.,HCoV-NL63).Recent studies have shown that some bat-circulating MERS-related coronaviruses(MERSr-CoVs),such as MOW15-22,PnNL2018B and HKU5,can use ACE2 to enter cells(Ma et al.,2025;Park et al.,2025).Even more worrying is that one novel bat-infecting merbecovirus HKU5-CoV lineage 2(BtHKU5-CoV-2)has been reported to use human ACE2 as a cell entry receptor(Chen et al.,2025).These ACE2-utilizing merbecoviruses expand the diversity,geographic distribution,and transmission potential of coronaviruses,posing a significant threat of spillover to humans.If an ACE2-utilizing MERSr-CoV acquire the high lethality of MERS-CoV and the high transmissibility of SARS-CoV-2 using ACE2 as a receptor,it could trigger a global pandemic with catastrophic consequences for humanity.Therefore,it is essential to evaluate serological cross-reactivity in sera from SARS-CoV-2-infected individuals against ACE2-using MERSr-CoVs,and urgent to develop preventive vaccines and pan-coronavirus antivirals confront the potential threat(Jiang and Wu,2025).
基金supported by the National Key Research and Development Program of China(2021YFD1800400)the National Natural Science Foundation of China(31872480)+1 种基金the Jiangsu Agriculture Science and Technology Innovation Fund,China(CX(19)2020)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD)。
文摘Streptococcus equi subsp.zooepidemicus(SEZ)is an important zoonotic agent.Here,a virulence-attenuated strain M35246 derived from natural variation of wild-type SEZ ATCC35246 was found.M35246 showed a deletion of 25contiguous genes as well as a loss-of-function mutation in covS.Subsequently,a 25-gene-deleted strain(ΔPI),a covS-mutant strain(Mcov S),and relevant complementary strains were constructed and investigated.M35246 and Mcov S were significantly less encapsulated and exhibited poorer anti-phagocytic capacity compared to wild-type SEZ.McovS was significantly more sensitive toβ-lactams,aminoglycosides,macrolides,and lincosamides than wild-type SEZ.M35246,McovS,andΔPI exhibited an increase in median lethal dose(LD_(50))in mice by 10~5,10~5,and 5 times when compared to wild-type SEZ,respectively.Neither M35246 nor McovS were isolated from mice 48 h after being challenged with approximately 2000 times the LD_(50)of wild-type SEZ.Transcriptome analysis showed that 668 significantly differentially expressed genes existed between McovS and wild-type SEZ.Numerous virulence factor-encoding genes and anabolicrelated genes in McovS that were involved in anti-phagocytosis,capsule formation,pathogenicity,and antibiotic resistance were downregulated significantly relative to the wild-type strain.This study revealed that the CovS plays a vital role in the establishment of SEZ virulence.
文摘In Streptococcus pyogenes, we have described the two-component signal transduction sensor and regulatory systems, CovR/S affect the antimicrobial susceptibility including penicillin G before. But the mechanism how two-component sensor protein CovS modulates penicillin G susceptibility has not been elucidated till date. This study aimed to determine how the CovS affected penicillin G susceptibility in Streptococcus pyogenes by northern blot analysis. At first, we investigated the covS mRNA expression under penicillin G induction. We found that the decrease of covS mRNA expression under Penicillin G stimulation. Next we investigated the expression of cell wall synthesis gene, pbp2a and glmM with use of covS knockout mutants from emm1 Streptococcus pyogenes strain 1529. We found that the cell-wall synthesis gene expression of the ?covS mutant strain were lower than that of the wild-type strain. Furthermore the expression of glmM mRNA gene was lower than the expression of pbp2a mRNA gene in the ?covS mutant strain. The covS-complemented strain almost restored the mRNA expression compared to covS mutant strain. The two-component sensor protein CovS affects the susceptibility to penicillin G in Streptococcus pyogenes by modulation of cell-wall synthesis.
文摘Background:Despite highly effective vaccines against SARS-CoV-2,COVID-19 vaccine hesitancy persisted in some populations in England during the pandemic,with rates and motivations for hesitancy varying by demographic group.Addressing the drivers of vaccine hesitancy through targeted interventions in hesitant groups is a public health priority for better and more rapid control of disease spread.We aimed to characterise the determinants and subtypes of vaccine hesitancy and identify more persistent forms of hesitancy via analysis of vaccine uptake in a large cross-sectional cohort with linked National Health Service(NHS)data.
基金supported by the Key Research and Development Program,Ministry of Science and Technology of the People’s Republic of China(Nos.2023YFC2606500,2023YFE0206500).
文摘Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.
基金supported by the Razi Vaccine and Serum Research Institute(RVSRI)Karaj,Iran,(No.17-18-18-063-01047-011130).
文摘Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.
基金National Key Research and Development Project of China(2023YFC2306600)Key Program of the National Natural Science Foundation of China(82430070)+6 种基金Shanghai Pujiang Program(No.23PJ1410800)National Natural Science Foundation of China(82072260,32370168)Eastern Talent Plan Leading Project,Shanghai Hospital Development Center Foundation(SHDC12022121)Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special(20Z11900900)Three-year Action Plan(2023-2025)Key Discipline Program on Public Health System Construction of Shanghai(GWVI-11.1-15)Construction of the Major Infectious Disease Medical Treatment System(GWVI-2.2).
文摘Dear Editor,The COVID-19 pandemic,caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in millions of deaths worldwide.It poses significant challenges in the management of immunocompromised patients,particularly people with HIV(PWH).Whether PWH are more vulnerable to COVID with more adverse outcomes has been extensively studied,but the findings are inconsistent.Many cohort studies and meta-analyses support that PWH have a higher risk of SARSCoV-2 infection and more severe COVID-19 outcomes(Bertagnolio et al.,2022;Ssentongo et al.,2021).
文摘目的筛选SARS病毒S蛋白的B细胞表位。方法使用SARS-CoV S DNA疫苗免疫BALB/c小鼠,获得SARS病毒S蛋白的免疫血清。人工合成包含169条部分氨基酸序列重叠的SARS-CoV S蛋白的多肽库。将多肽片段包被ELISA板,利用免疫小鼠血清,通过抗体结合试验来筛选SARS病毒S蛋白的线性B细胞表位。并将筛选结果与使用B细胞表位分析软件预测的结果进行比较。结果使用重叠肽合成法筛选到SARS-CoV蛋白两条多肽片段S335-352和S442-458,能与免疫动物血清特异性结合,与使用Bcipep数据库预测B细胞表位的结果相一致。结论鉴定了两个新的SARS病毒S蛋白B细胞表位。
