In 2008,China launched a national surveillance system for hand‐foot‐and‐mouth disease(HFMD).Several million cases of HFMD are reported every year,coxsackievirus A16(CVA16)was the leading cause of HFMD epidemic in Y...In 2008,China launched a national surveillance system for hand‐foot‐and‐mouth disease(HFMD).Several million cases of HFMD are reported every year,coxsackievirus A16(CVA16)was the leading cause of HFMD epidemic in Yantai city,China in recent years,but the information of epidemiology and molecular characterization of CVA16 in Yantai is limited.The aim of this study is to investigate the epidemiological characteristics and pathogenic spectrum of HFMD,and most importantly,the molecular characterization of CVA16 in Yantai from 2018 to 2021.A total of 2,000 clinical samples were collected in Yantai city from 2018 to 2021 and the enterovirus typing was performed using real‐time reverse transcriptase–polymerase chain reaction(qRT‐PCR).VP1 coding regions of 41 CVA16 isolates were amplified and Sanger sequenced,and phylogenetic analysis was performed.During the study period,HFMD became prevalent from May to August each year.It peaked in June and declined in September.The incidence was highest in children aged 1 to 5 years,while more common in males than females.1,617 out of 2,000 clinical collection of samples were tested positive for enterovirus.Among them,614 were identified as CVA16,45 were enterovirus A71(EV A17),and 958 were other enterovirus serotypes.All 41 CVA16 strains belonged to the Bla and B1b genotypes.Homology analysis showed that 41 CVA16 isolates shared 83.2%–100%nucleotide and 93.7%–100%amino acid similarity among themselves.The results of this study update molecular epidemiology of CVA16 and provide a reference for HFMD prevention and control.展开更多
Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds ch...Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds children＇s death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were： to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course. Methods Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively. Results Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% （106/133） and 92.5% （123/133）, respectively; geometric mean titers （GMTs） were 29.0 and 61.9; 75.9% （101/133） prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% （34/133） and 38.3% （51/133） in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months （82.6） compared with that at two months （P 〈0.05）, showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring （0.75%） at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months. Conclusions The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.展开更多
Background Coxsackievirus A16(CVA16)is one of the major etiological agents of hand,foot and mouth discase(HFMD).This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16.Meth...Background Coxsackievirus A16(CVA16)is one of the major etiological agents of hand,foot and mouth discase(HFMD).This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16.Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010-2019.Enteroviruses(EVs)were detected and typed by real-ime reverse transcription-polymerase chain reaction(RT-PCR)and RT-PCR.The genotype,evolutionary rate,the most recent common ancestor,population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene(VPI)by bioinformatics software.Results A total of 4709 throat swabs were screened.EVs were detected in 3180 samples and 814 were CVA16 positive.More than 81%of CVA 16-positive children were under 5 years old.The prevalence of CVA 16 showed obvious periodic fluctuations with a high level during 2010--2012 followed by an apparent decline during 2013--2017.However,the activities of CVA16 increased gradually during 2018-2019.All the Beijing CVA16 strains belonged to sub-genotype BI,and B Ib was the dominant strain.One B Ic strain was detected in Bejing for the first time in 2016.The estimated mean evolutionary rate of VPI gene was 4.49x 103 substitution/site/year.Methionine gradually fixed at site-23 of VP1 since 2012.Two sites were detected under episodic positive selection,one of which(site-223)located in neutralizing linear epitope PEP71.Conclusions The dominant strains of CVA 16 belonged to clade B lb and evolved in a fast evolutionary rate during 2010-2019 in Beiing.To provide more favorable data for HFMD prevention and control,it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.展开更多
Coxsackievirus A16 belongs to the family Picornaviridae,and is a major agent of hand-foot-and-mouth disease that infects mostly children,and to date no vaccines or antivi-ral therapies are available.2A protease of ent...Coxsackievirus A16 belongs to the family Picornaviridae,and is a major agent of hand-foot-and-mouth disease that infects mostly children,and to date no vaccines or antivi-ral therapies are available.2A protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4G.Here we present the crystal structure of coxsackievirus A162A protease,which interestingly forms hexamers in crystal as well as in solution.This structure shows an open conformation,with its active site accessible,ready for substrate binding and cleav-age activity.In conjunction with a previously reported“closed”state structure of human rhinovirus 2,we were able to develop a detailed hypothesis for the conforma-tional conversion triggered by two“switcher”residues Glu88 and Tyr89 located within the bll2-cII loop.Substrate recognition assays revealed that amino acid residues P1′,P2 and P4 are essential for substrate specificity,which was verifi ed by our substrate binding model.In addition,we compared the in vitro cleavage effi ciency of 2A pro-teases from coxsackievirus A16 and enterovirus 71 upon the same substrates by fl uorescence resonance energy transfer(FRET),and observed higher protease activity of enterovirus 71 compared to that of coxsackievirus A16.In conclusion,our study shows an open conformation of coxsackievirus A162A protease and the underlying mechanisms for conformational conversion and substrate specifi city.These new insights should facilitate the future rational design of effi cient 2A protease inhibitors.展开更多
Dear Editor,Coxsackievirus A16(CA16)is one of the major viral pathogens associated with hand,foot,and mouth disease.CA16 belongs to the Enterovirus genus of the Picornaviridae family and possesses a single-stranded po...Dear Editor,Coxsackievirus A16(CA16)is one of the major viral pathogens associated with hand,foot,and mouth disease.CA16 belongs to the Enterovirus genus of the Picornaviridae family and possesses a single-stranded positivesense RNA genome(Mao et al.,2014).Reverse genetics is an important tool for CA16 research.Previously,a reverse genetics T7 polymerase-based system was de-展开更多
Dear Editor,Coxsackievirus A16(CV A16)and enterovirus 71(EV71)are currently the two primary causative agents of handfoot-and-mouth disease(HFMD)(Solomon et al.,2010;Mao et al.,2014),threatening health of children worl...Dear Editor,Coxsackievirus A16(CV A16)and enterovirus 71(EV71)are currently the two primary causative agents of handfoot-and-mouth disease(HFMD)(Solomon et al.,2010;Mao et al.,2014),threatening health of children worldwide.They both belong to the Enterovirus genus of展开更多
Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can...Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.展开更多
Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clini...Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD.Serum cholinesterase(SChE)activity has frequently been reported as a potential biomarker for solid central nervous system tumors,chronic heart failure,and liver cirrhosis.However,its potential value in the diagnosis of neurotropic virus infections,such as HFMD caused by EV71,remains to be determined.Findings:In our study,220 children hospitalized with HFMD caused by EV71,34 inpatients infected with coxsackievirus A16(CVA16),and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children’s Hospital between January 2011 and December 2012.SChE activity was measured.The non-parametric Mann–Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls(p<0.001),as well as in children with upper respiratory tract infections(p=0.011),bronchopneumonia(p<0.001),septicemia(p<0.001),amygdalitis(p<0.001),and appendicitis(p<0.001).In addition,higher SChE activity was observed in male inpatients with HFMD caused by EV71(47.7%positivity)compared to female inpatients(26.1%positivity)(chi-square test,p=0.002).In our study,no significant differences in SChE levels were observed among different ages(up to 120 months)(r=-0.112,p>0.05).An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase(p<0.001).Conclusions:Elevated SChE activity was observed in patients with severe HFMD caused by EV71.Therefore,SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.展开更多
In this paper, cinobufagin and resibufogenin were found to inhibit enterovirus 71（EV71） infection in vitro in cell viability and plaque reduction assays. The 50% inhibitory concentrations（lCs0） of einobufagin and ...In this paper, cinobufagin and resibufogenin were found to inhibit enterovirus 71（EV71） infection in vitro in cell viability and plaque reduction assays. The 50% inhibitory concentrations（lCs0） of einobufagin and resibufoge- nin were （10.94±2.36） and （218±31） nmol/L, respectively, the 50% cytotoxic concentrations（CCs0） of them were （1277±223） and （1385±254） nmol/L, respectively, and the anti-EV71 selectivity index（SI50） of cinobufagin was 116.7, which are promisingly developed into drug. Using a VP1 detection assay and a constructed reporter luciferase, we found that cinobufagin and resibufogenin disrupted the synthesis of EV71 protein. However, neither of them inhibited EV71 RNA replication. Our study suggests that cinobufagin and resibufogenin are the promising candidates that should he fllrther investigated for the treatment of EV71 caused disease.展开更多
基金supported by Shandong Provincial Preventive Medicine Association Project(LYH 2017‐26).
文摘In 2008,China launched a national surveillance system for hand‐foot‐and‐mouth disease(HFMD).Several million cases of HFMD are reported every year,coxsackievirus A16(CVA16)was the leading cause of HFMD epidemic in Yantai city,China in recent years,but the information of epidemiology and molecular characterization of CVA16 in Yantai is limited.The aim of this study is to investigate the epidemiological characteristics and pathogenic spectrum of HFMD,and most importantly,the molecular characterization of CVA16 in Yantai from 2018 to 2021.A total of 2,000 clinical samples were collected in Yantai city from 2018 to 2021 and the enterovirus typing was performed using real‐time reverse transcriptase–polymerase chain reaction(qRT‐PCR).VP1 coding regions of 41 CVA16 isolates were amplified and Sanger sequenced,and phylogenetic analysis was performed.During the study period,HFMD became prevalent from May to August each year.It peaked in June and declined in September.The incidence was highest in children aged 1 to 5 years,while more common in males than females.1,617 out of 2,000 clinical collection of samples were tested positive for enterovirus.Among them,614 were identified as CVA16,45 were enterovirus A71(EV A17),and 958 were other enterovirus serotypes.All 41 CVA16 strains belonged to the Bla and B1b genotypes.Homology analysis showed that 41 CVA16 isolates shared 83.2%–100%nucleotide and 93.7%–100%amino acid similarity among themselves.The results of this study update molecular epidemiology of CVA16 and provide a reference for HFMD prevention and control.
文摘Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds children＇s death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were： to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course. Methods Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively. Results Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% （106/133） and 92.5% （123/133）, respectively; geometric mean titers （GMTs） were 29.0 and 61.9; 75.9% （101/133） prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% （34/133） and 38.3% （51/133） in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months （82.6） compared with that at two months （P 〈0.05）, showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring （0.75%） at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months. Conclusions The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.
基金supported by the Key Technologies R&D Program of the National Ministry of Science(2018ZX10713001-003)the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTCX201822)the National Natural Science Foundation of China(81350019).
文摘Background Coxsackievirus A16(CVA16)is one of the major etiological agents of hand,foot and mouth discase(HFMD).This study aimed to investigate the molecular epidemiology and evolutionary characteristics of CVA16.Methods Throat swabs were collected from children with HFMD and suspected HFMD during 2010-2019.Enteroviruses(EVs)were detected and typed by real-ime reverse transcription-polymerase chain reaction(RT-PCR)and RT-PCR.The genotype,evolutionary rate,the most recent common ancestor,population dynamics and selection pressure of CVA16 were analyzed based on viral protein gene(VPI)by bioinformatics software.Results A total of 4709 throat swabs were screened.EVs were detected in 3180 samples and 814 were CVA16 positive.More than 81%of CVA 16-positive children were under 5 years old.The prevalence of CVA 16 showed obvious periodic fluctuations with a high level during 2010--2012 followed by an apparent decline during 2013--2017.However,the activities of CVA16 increased gradually during 2018-2019.All the Beijing CVA16 strains belonged to sub-genotype BI,and B Ib was the dominant strain.One B Ic strain was detected in Bejing for the first time in 2016.The estimated mean evolutionary rate of VPI gene was 4.49x 103 substitution/site/year.Methionine gradually fixed at site-23 of VP1 since 2012.Two sites were detected under episodic positive selection,one of which(site-223)located in neutralizing linear epitope PEP71.Conclusions The dominant strains of CVA 16 belonged to clade B lb and evolved in a fast evolutionary rate during 2010-2019 in Beiing.To provide more favorable data for HFMD prevention and control,it is necessary to keep attention on molecular epidemiological and evolutionary characteristics of CVA16.
基金the National Basic Research Program(973 Program)(Nos.2014CB542800 and 2011CB915501)the National Natural Science Foundation of China(Grant No.31170702).
文摘Coxsackievirus A16 belongs to the family Picornaviridae,and is a major agent of hand-foot-and-mouth disease that infects mostly children,and to date no vaccines or antivi-ral therapies are available.2A protease of enterovirus is a nonstructural protein and possesses both self-cleavage activity and the ability to cleave the eukaryotic translation initiation factor 4G.Here we present the crystal structure of coxsackievirus A162A protease,which interestingly forms hexamers in crystal as well as in solution.This structure shows an open conformation,with its active site accessible,ready for substrate binding and cleav-age activity.In conjunction with a previously reported“closed”state structure of human rhinovirus 2,we were able to develop a detailed hypothesis for the conforma-tional conversion triggered by two“switcher”residues Glu88 and Tyr89 located within the bll2-cII loop.Substrate recognition assays revealed that amino acid residues P1′,P2 and P4 are essential for substrate specificity,which was verifi ed by our substrate binding model.In addition,we compared the in vitro cleavage effi ciency of 2A pro-teases from coxsackievirus A16 and enterovirus 71 upon the same substrates by fl uorescence resonance energy transfer(FRET),and observed higher protease activity of enterovirus 71 compared to that of coxsackievirus A16.In conclusion,our study shows an open conformation of coxsackievirus A162A protease and the underlying mechanisms for conformational conversion and substrate specifi city.These new insights should facilitate the future rational design of effi cient 2A protease inhibitors.
基金supported by grants from the Science and Technology Commission of Shanghai Municipality (13ZR1462900)the Shanghai Institutes for Biological Science (SIBS),Chinese Academy of Science (CAS) (2013KIP317)+1 种基金the support of the SA-SIBS scholarship programYouth Innovation Promotion Association of CAS (2016249)
文摘Dear Editor,Coxsackievirus A16(CA16)is one of the major viral pathogens associated with hand,foot,and mouth disease.CA16 belongs to the Enterovirus genus of the Picornaviridae family and possesses a single-stranded positivesense RNA genome(Mao et al.,2014).Reverse genetics is an important tool for CA16 research.Previously,a reverse genetics T7 polymerase-based system was de-
文摘Dear Editor,Coxsackievirus A16(CV A16)and enterovirus 71(EV71)are currently the two primary causative agents of handfoot-and-mouth disease(HFMD)(Solomon et al.,2010;Mao et al.,2014),threatening health of children worldwide.They both belong to the Enterovirus genus of
基金supported by the National Science and Technology Major Project of China(No.2018ZX10201001-010,No.2017ZX10103009-005,No.2018ZX10713001-007)the National Natural Science Fund for Distinguished Young Scholars of China(No.81525023)+4 种基金the National Natural Science Foundation of China(No.81473031)the Program of Shanghai Academic/Technology Research Leader(No.18XD1400300)the Li Ka Shing Oxford Global Health Programme(No.B9RST00-B900.57)the Chinese Preventive Medicine Association(No:20101801)supported by CAS Pioneer Hundred Talents Program
文摘Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.
基金supported by the National Natural Science Foundation of China(No:81271826).
文摘Background:Hand,foot,and mouth disease(HFMD)caused by enterovirus 71(EV71)is a potentially life-threatening infectious disease that commonly occurs in children.Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD.Serum cholinesterase(SChE)activity has frequently been reported as a potential biomarker for solid central nervous system tumors,chronic heart failure,and liver cirrhosis.However,its potential value in the diagnosis of neurotropic virus infections,such as HFMD caused by EV71,remains to be determined.Findings:In our study,220 children hospitalized with HFMD caused by EV71,34 inpatients infected with coxsackievirus A16(CVA16),and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children’s Hospital between January 2011 and December 2012.SChE activity was measured.The non-parametric Mann–Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls(p<0.001),as well as in children with upper respiratory tract infections(p=0.011),bronchopneumonia(p<0.001),septicemia(p<0.001),amygdalitis(p<0.001),and appendicitis(p<0.001).In addition,higher SChE activity was observed in male inpatients with HFMD caused by EV71(47.7%positivity)compared to female inpatients(26.1%positivity)(chi-square test,p=0.002).In our study,no significant differences in SChE levels were observed among different ages(up to 120 months)(r=-0.112,p>0.05).An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase(p<0.001).Conclusions:Elevated SChE activity was observed in patients with severe HFMD caused by EV71.Therefore,SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.
文摘In this paper, cinobufagin and resibufogenin were found to inhibit enterovirus 71（EV71） infection in vitro in cell viability and plaque reduction assays. The 50% inhibitory concentrations（lCs0） of einobufagin and resibufoge- nin were （10.94±2.36） and （218±31） nmol/L, respectively, the 50% cytotoxic concentrations（CCs0） of them were （1277±223） and （1385±254） nmol/L, respectively, and the anti-EV71 selectivity index（SI50） of cinobufagin was 116.7, which are promisingly developed into drug. Using a VP1 detection assay and a constructed reporter luciferase, we found that cinobufagin and resibufogenin disrupted the synthesis of EV71 protein. However, neither of them inhibited EV71 RNA replication. Our study suggests that cinobufagin and resibufogenin are the promising candidates that should he fllrther investigated for the treatment of EV71 caused disease.
