Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infect...Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.展开更多
Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new ...Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in great demand. The present study was performed to investigate the anti-HBV activity of epigallocatechin- 3-gallate （EGCG）, a natural-origin compound, in HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the levels of HBsAg and HBeAg in the supematant and extracellular HBV DNA. EGCG effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose- and time-dependent manner, and it showed stronger effects at the level of 0.11-0.44 pmol/ml （50-200 μg/ml） than lamivudine （3TC） at 0.87 μmol/ml （200 pg/ml）. EGCG also suppressed the amount of extracellular HBV DNA. The data indicated that EGCG possessed anti-HBV activity and suggested the potential of EGCG as an effective anti-HBV agent with low toxicity.展开更多
Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral infection.However,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,...Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral infection.However,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical application.In this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus replication.FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection.Mechanistically,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through interaction.Reduced IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA treatment.In FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus infection.Thus,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon signaling.Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.展开更多
Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 4...Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.展开更多
A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cuc...A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cucumber mosaic virus（CMV） in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/m L, which was superior to ningnanmycin（409.3 mg/m L）.展开更多
AIM： To investigate whether DNA-dependent activator of interferon-regulatory factors （DAI） inhibits hepatitis B virus （HBV） replication and what the mechanism is. METHODS： After the human hepatoma cell line Huh7...AIM： To investigate whether DNA-dependent activator of interferon-regulatory factors （DAI） inhibits hepatitis B virus （HBV） replication and what the mechanism is. METHODS： After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plas- mid, viral protein （HBV surface antigen and HBV e an- tigen） secretion was detected by enzyme-linked immu- nosorbent assay, and HBV RNA was analyzed by real- time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 （IRF3） phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-KB （NF-KB） activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Tran- swell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS： Viral protein secretion was significantly re- duced by 57% （P 〈 0.05）, and the level of total HBV RNA was reduced by 67% （P 〈 0.05）. The viral core particle-associated DNA was also dramatically down- regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-KB signaling was essential for DAI to elicit antivi- ral response in Huh7 cells. When the NF-KB signaling pathway was blocked by a NF-KB signaling suppressor （I~：B^-SR）, the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was indepen- dent of IRF3 signaling and secreted cytokines. CONCLUSION： This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is asso- ciated with activation of NF-KB but independent of IRF3 and secreted cytokines.展开更多
The title compound S-（＋）-N＇-tertbutylaminocarbonyl-N-[3-methyl-2-（4-chlorophenyl）butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There...The title compound S-（＋）-N＇-tertbutylaminocarbonyl-N-[3-methyl-2-（4-chlorophenyl）butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There exist intramolecular N（2）-H（2A）…O（1）, C（17）-H（17A）… O（2） and N（3）-H（3A）…S（1） hydrogen bonds as well as intermolecular N-H…O interaction between the carbonyl and amidogen groups. Crystallographic data： CITH24ClN3O2S, Mr = 369.90, monoclinic, space group C2/c with a = 22.9922（19）, b = 14.4844（12）, c = 12.4618（11） A, β = 92.608（2）°, V = 4145.8（6） ]k3, Z = 8, Dc = 1.185 g/cm^3, F（000） = 1568, g（MoKa） = 0.298 mm^-1, R = 0.0578 and wR = 0.1308.展开更多
Coxsackievirus B type 3(CVB3)is one of the major causative pathogens associated with viral meningitis and myocarditis,which are widespread in the human population and especially prevalent in neonates and children.Thes...Coxsackievirus B type 3(CVB3)is one of the major causative pathogens associated with viral meningitis and myocarditis,which are widespread in the human population and especially prevalent in neonates and children.These infections can result in dilated cardiomyopathy(DCM)and other severe clinical complications.There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases.During screening for anti-CVB3 candidates in our previous studies,we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses(CVBs).The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C.Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner.Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3.We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins,finding that jiadifenoic acids C could reduce VP1 and 3D protein production.A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation,indicating that jiadifenoic acids C functioned at an early step of CVB3 replication.However,jiadifenoic acids C had no prophylactic effect against CVB3.Taken together,we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB,including the pleconaril-resistant variant.Our study could provide a significant lead for anti-CVB3 drug development.展开更多
Two unprecedented polycyclic spirooliganones C and D(1 and 2)with a novel spiro[bicyclo[2.2.2]octane-2,2′-bicyclo[3.1.0]hexane]carbon skeleton,one known dimeric prenylated C_(6)single bondC_(3)compound(3),and a pair ...Two unprecedented polycyclic spirooliganones C and D(1 and 2)with a novel spiro[bicyclo[2.2.2]octane-2,2′-bicyclo[3.1.0]hexane]carbon skeleton,one known dimeric prenylated C_(6)single bondC_(3)compound(3),and a pair of new enantiomeric prenylated C_(6)single bondC_(3)compounds(+)-5 and(−)-5 together with their direct precursors(+)-4 and(−)-4 were isolated from the roots of Illicium oligandrum.Their structures and absolute configurations were elucidated by spectroscopic analysis,single crystal X-ray diffraction data,and electronic circular dichroism calculations.A possible biosynthetic pathway for compounds 1 and 2 involving the Diels-Alder reaction between(−)-sabinene and cyclic prenylated tetrahydropyrano-type C_(6)single bondC_(3)compounds was proposed.The characteristic prenylated C_(6)single bondC_(3)compounds(+)-4 and(−)-4 were separated on a chiral stationary phase and their absolute configurations were determined by calculated ECD for the first time.In the antiviral bioassays,compounds 1 and(+)-5 exhibited significant inhibitory activity against CVB3 with IC_(50)values of 11.11μmol/L and 1.11μmol/L,respectively.Compounds 1 and 2 also showed moderate inhibition against influenza A(H1N1)virus.展开更多
文摘Dear Editor, The 2015-2016 outbreak of Zika virus （ZIKV） fever, first reported in Brazil during early 2015 （Zanluca et al., 2015）, has infected millions of people and is a global public health concern. ZIKV infections are associated with fetal microcephaly, as well as neurological complications in humans. The virus can be shed in the semen and vaginal secretions of humans, leading to sexual transmission, and unexpectedly ZIKV infections cause severe damage to the male reproductive organs in male mice （Govero et al., 2016; Ma et al., 2016）.
基金Project supported by the National Commonweal Industry Special Research Foundation of China(No.200807020)the National Natural Science Foundation of China(Nos.30973947 and 81173571)
文摘Although several antiviral drugs and vaccines are available for use against hepatitis B virus （HBV）, hepatitis caused by HBV remains a major public health problem worldwide, which has not yet been resolved, and new anti-HBV drugs are in great demand. The present study was performed to investigate the anti-HBV activity of epigallocatechin- 3-gallate （EGCG）, a natural-origin compound, in HepG2 2.2.15 cells. The antiviral activity of EGCG was examined by detecting the levels of HBsAg and HBeAg in the supematant and extracellular HBV DNA. EGCG effectively suppressed the secretion of HBsAg and HBeAg from HepG2 2.2.15 cells in a dose- and time-dependent manner, and it showed stronger effects at the level of 0.11-0.44 pmol/ml （50-200 μg/ml） than lamivudine （3TC） at 0.87 μmol/ml （200 pg/ml）. EGCG also suppressed the amount of extracellular HBV DNA. The data indicated that EGCG possessed anti-HBV activity and suggested the potential of EGCG as an effective anti-HBV agent with low toxicity.
基金supported by the National Natural Science Foundation(NNSF)of China(Nos.82371774 and 81901613)Beijing Nova Program(20230484342,China)Natural Science Foundation of Guangdong Province(2020A1515011299,China).
文摘Bile acids(BAs)are natural metabolites in mammals and have the potential to function as drugs against viral infection.However,the limited understanding of chenodeoxycholic acid(CDCA)receptors and downstream signaling,along with its lower suppression efficiency in inhibiting virus infection limits its clinical application.In this study,we demonstrate that farnesoid X receptor(FXR),the receptor of CDCA,negatively regulates interferon signaling,thereby contributing to the reduced effectiveness of CDCA against virus replication.FXR deficiency or pharmacological inhibition enhances interferon signaling activation to suppress virus infection.Mechanistically,FXR impairs the DNA binding and transcriptional abilities of activated interferon regulatory factor 3(IRF3)through interaction.Reduced IRF3 transcriptional activity by FXReIRF3 interaction significantly undermines the expression of Interferon Beta 1(IFNB1)and the antiviral response of cells,especially upon the CDCA treatment.In FXR-deficient cells,or when combined with Z-guggulsterone(GUGG)treatment,CDCA exhibits a more potent ability to restrict virus infection.Thus,these findings suggest that FXR serves as a limiting factor for CDCA in inhibiting virus replication,which can be attributed to the“signaling-brake”roles of FXR in interferon signaling.Targeting FXR inhibition represents a promising pharmaceutical strategy for the clinical application of BAs metabolites as antiviral drugs.
基金supported by the National Natural Science Foundation of China(Grant Number 32260370)Youth Talent Project of Major Academic and Technical Leaders Training Program of Jiangxi Province(Grant Number 20204BCJL23045)+2 种基金Special Research Project on Camphor Tree(KRPCT)of Jiangxi Forestry Department(Grant Number 2020CXZX07)Innovative Leading Talent Short-Term Project in Natural Science Area of Jiangxi Province(Grant Number jxsq2018102072)the Key Research and Development Program of Jiangxi Province(Grant Number 20192BBFL60014).
文摘Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.
基金assistance from the National Natural Science Foundation of China (No. 21302025)the Special Funds for Training object of Outstanding Young Scientific & Technological Talents in Guizhou Province (No. 2015-15#)the Science & Technology Foundation of Guizhou Province (No. J[2014]2056#)
文摘A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cucumber mosaic virus（CMV） in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/m L, which was superior to ningnanmycin（409.3 mg/m L）.
基金Supported by Grants of The Chinese State Basic Research, No.2009CB522504National Mega Projects for Infectious Diseases, No. 2008ZX10203
文摘AIM： To investigate whether DNA-dependent activator of interferon-regulatory factors （DAI） inhibits hepatitis B virus （HBV） replication and what the mechanism is. METHODS： After the human hepatoma cell line Huh7 was cotransfected with DAI and HBV expressing plas- mid, viral protein （HBV surface antigen and HBV e an- tigen） secretion was detected by enzyme-linked immu- nosorbent assay, and HBV RNA was analyzed by real- time polymerase chain reaction and Northern blotting, and viral DNA replicative intermediates were examined by Southern blotting. Interferon regulatory factor 3 （IRF3） phosphorylation and nuclear translocation were analyzed via Western blotting and immunofluorescence staining respectively. Nuclear factor-KB （NF-KB） activity induced by DAI was detected by immunofluorescence staining of P65 and dual luciferase reporter assay. Tran- swell co-culture experiment was performed in order to investigate whether the antiviral effects of DAI were dependent on the secreted cytokines. RESULTS： Viral protein secretion was significantly re- duced by 57% （P 〈 0.05）, and the level of total HBV RNA was reduced by 67% （P 〈 0.05）. The viral core particle-associated DNA was also dramatically down- regulated in DAI-expressing Huh7 cells. Analysis of involved signaling pathways revealed that activation of NF-KB signaling was essential for DAI to elicit antivi- ral response in Huh7 cells. When the NF-KB signaling pathway was blocked by a NF-KB signaling suppressor （I~：B^-SR）, the anti-HBV activity of DAI was remarkably abrogated. The inhibitory effect of DAI was indepen- dent of IRF3 signaling and secreted cytokines. CONCLUSION： This study demonstrates that DAI can inhibit HBV replication and the inhibitory effect is asso- ciated with activation of NF-KB but independent of IRF3 and secreted cytokines.
基金This work was supported by the National Key Technologies R & D Programs of China (No. 2004BA-308A22-8)
文摘The title compound S-（＋）-N＇-tertbutylaminocarbonyl-N-[3-methyl-2-（4-chlorophenyl）butyryl] thiourea has been synthesized and its crystal structure was determined by singlecrystal X-ray diffraction analysis. There exist intramolecular N（2）-H（2A）…O（1）, C（17）-H（17A）… O（2） and N（3）-H（3A）…S（1） hydrogen bonds as well as intermolecular N-H…O interaction between the carbonyl and amidogen groups. Crystallographic data： CITH24ClN3O2S, Mr = 369.90, monoclinic, space group C2/c with a = 22.9922（19）, b = 14.4844（12）, c = 12.4618（11） A, β = 92.608（2）°, V = 4145.8（6） ]k3, Z = 8, Dc = 1.185 g/cm^3, F（000） = 1568, g（MoKa） = 0.298 mm^-1, R = 0.0578 and wR = 0.1308.
基金This work was supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(2012ZX09301002-001-015 and 2012ZX10004501-004-001).
文摘Coxsackievirus B type 3(CVB3)is one of the major causative pathogens associated with viral meningitis and myocarditis,which are widespread in the human population and especially prevalent in neonates and children.These infections can result in dilated cardiomyopathy(DCM)and other severe clinical complications.There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases.During screening for anti-CVB3 candidates in our previous studies,we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses(CVBs).The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C.Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner.Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3.We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins,finding that jiadifenoic acids C could reduce VP1 and 3D protein production.A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation,indicating that jiadifenoic acids C functioned at an early step of CVB3 replication.However,jiadifenoic acids C had no prophylactic effect against CVB3.Taken together,we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB,including the pleconaril-resistant variant.Our study could provide a significant lead for anti-CVB3 drug development.
基金supported by grants from the National Natural Science Foundation of China(Nos.21732008 and 22177135)。
文摘Two unprecedented polycyclic spirooliganones C and D(1 and 2)with a novel spiro[bicyclo[2.2.2]octane-2,2′-bicyclo[3.1.0]hexane]carbon skeleton,one known dimeric prenylated C_(6)single bondC_(3)compound(3),and a pair of new enantiomeric prenylated C_(6)single bondC_(3)compounds(+)-5 and(−)-5 together with their direct precursors(+)-4 and(−)-4 were isolated from the roots of Illicium oligandrum.Their structures and absolute configurations were elucidated by spectroscopic analysis,single crystal X-ray diffraction data,and electronic circular dichroism calculations.A possible biosynthetic pathway for compounds 1 and 2 involving the Diels-Alder reaction between(−)-sabinene and cyclic prenylated tetrahydropyrano-type C_(6)single bondC_(3)compounds was proposed.The characteristic prenylated C_(6)single bondC_(3)compounds(+)-4 and(−)-4 were separated on a chiral stationary phase and their absolute configurations were determined by calculated ECD for the first time.In the antiviral bioassays,compounds 1 and(+)-5 exhibited significant inhibitory activity against CVB3 with IC_(50)values of 11.11μmol/L and 1.11μmol/L,respectively.Compounds 1 and 2 also showed moderate inhibition against influenza A(H1N1)virus.
