Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as ...Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.展开更多
Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predicto...Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.展开更多
Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges pos...Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.展开更多
Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory sym...Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.展开更多
Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegment...Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.展开更多
BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of d...BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of direct-acting antiviral(DAA)treatment in HCV-infected patients.METHODS The study included consecutive 9457 women and 9529 men,treated with DAA for chronic HCV infection from July 2015 to the end of 2023 whose data were collected in the nationwide multicenter retrospective Epiter-2 project.Women were divided into pre-menopausal(15-44 years),menopausal(45-55 years)and post-menopausal(>55 years)and compared with age-matched men.RESULTS Regardless of age,women had a significantly lower body mass index,prevalence of genotype 3 infection and proportion of cirrhosis compared to men.Psychiatric disorders(except depression),hepatitis B virus and human immunodeficiency virus co-infections,as well as alcohol and drug addiction,were significantly less common in women than in men in all age groups.The sustained virologic response was significantly higher in women compared to men in each age group and amounted to 98.4%and 96.6%,respectively(P<0.001).Independent predictors of treatment failure in women were genotype 3 infection,cirrhosis and postmenopausal age.Mild adverse events were reported significantly more often by women,regardless of age with the highest percentage in the postmenopausal group.CONCLUSION DAA treatment is more effective in women than in men,regardless of age,but in postmenopausal women,the effectiveness is relatively the lowest.展开更多
In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B ...In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.展开更多
Herein,we report the first asymmetric synthesis of illihenin A,an antiviral sesquiterpenoid bearing a cage-like tricyclo[6.2.2.01,5]dodecane skeleton.Starting from an abundant feedstock(-)-α-cedrene,this19-step synth...Herein,we report the first asymmetric synthesis of illihenin A,an antiviral sesquiterpenoid bearing a cage-like tricyclo[6.2.2.01,5]dodecane skeleton.Starting from an abundant feedstock(-)-α-cedrene,this19-step synthesis approach features a novel ring-reorganization strategy that includes early stage C7-hydroxylation of the cedrane skeleton and a later-stage ring disassembly-reassembly procedure,affording the desired product with high synthetic efficiency and minimal chiral manipulation.The key transformations include the following:(i)a hydroxy group-directed SmI2-mediated reductive coupling to construct the congested tertiary 7-OH cedrane,(ii)aβ-fragmentation triggered by an alkoxy radical to release a spiro[4.5]decane,and(iii)an intramolecular Aldol reaction,concomitant withα-epimerization,to furnish the tricyclic framework.In addition,preliminary investigation of antiviral activity against CVB3 revealed that illihenin A can significantly inhibit ROS production and apoptosis.展开更多
The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations.This widespread occurrence of multiple viral diseases in pig farms has in...The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations.This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry.Consequently,there is an urgent need for eco-friendly and efficient antivi-ral drugs that can effectively combat viruses and prevent diseases such as PEDV,PRRSV,PRV,and other viral infections.To this end,we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts(CHE) against PRV.In vitro testing of several extracts,namely,Echinacea,Ilex purpurea Hassk,Ganoderma lucidum Kars,Taraxacum mongolicum,and Ilex rotunda Thunb,exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects.Specifically,their antiviral selectivity indexes were significantly higher,with values ranging from 6-to 144-fold.The antiviral efficacy of five CHEs was evaluated against other RNA viruses,including PRRSV and PEDV.The extracts showed substantial inhibition of PEDV and PRRSV proliferation.Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects.To understand the antiviral mechanisms underlying their potent activity,a time-of-addition experiment was conducted.The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV,PEDV,and PRRSV.The study found that the Chinese herbal extracts,Echinacea and Ilex purpurea Hassk,had both direct and indirect effects on virus particles and cellular targets,demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV.These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV,PEDV and PRRSV in the swine industry.The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions.展开更多
BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often ci...BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often cited as a concern when initiating treatment.Hepatitis B treatment adherence in the context of the patient’s medical and life experiences remains underexplored.AIM To evaluate factors associated with adherence to hepatitis B oral antiviral treatment.METHODS A global online survey was administered anonymously to adults(aged 18 years or older)living with chronic hepatitis B.A subsample of 614 individuals who reported being on hepatitis B treatment was included in the analysis.Indices for treatment affordability,healthcare service acceptability,and individual physical,psychological,and emotional functioning were constructed(Cronbach’s alpha=0.71-0.83).Data analysis was conducted using Stata/BE 17.0.RESULTS Overall,81%of respondents reported high adherence to hepatitis B treatment.Lower adherence was observed among individuals who identified as African or African American(P=0.008).Among participants with low adherence,60%cited affordability as a challenge(P=0.068),53%identified healthcare service acceptability as a challenge(P=0.04),79%described physical functioning as a challenge(P=0.002),and 40.5%reported difficulties with psychological functioning(P=0.55).CONCLUSION Findings demonstrate high treatment adherence,although access to and acceptability of healthcare services,as well as an individual’s physical functioning challenges,appear to be related to low adherence.展开更多
Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical c...Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.展开更多
Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing metho...Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing methodologies rooted in molecular biology and virology,such as viral infection and FACS,the effect of ulvan on virus infection and the innate immune responses in cells were evaluated.Results Ulvan significantly restricted vesicular stomatitis virus(VSV)infection.Preliminary exploration on its mechanism indicated that ulvan activated the innate immune,and induced type I interferons(IFN-Ⅰ)expression to restrict viral infection.展开更多
Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines....Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines.However,the absence of reference TBEV strains in the country presented a major challenge.To address this,we generated a prototype strain(Vasilchenko)of the Siberian TBEV genotype,predominant in Kazakhstan,using synthetic genome and molecular infectious clone technology.A DNA-launched TBEV molecular clone was assembled from DNA fragments,enabling virus rescue upon plasmid transfection.During the propagation of the post-transfection virus in cell culture,a single amino acid substitution(E51K)in the envelope protein emerged,resulting in a 100-fold increase in the titer of the mutant variant.In vivo,this mutation significantly attenuated virulence:while wild-type TBEV caused 100%mortality in BALB/c mice,the E51K variant was non-lethal and exhibited reduced viremia,suggesting impaired neuroinvasiveness.To further exploit this attenuated,high-titer virus,we developed a GFP-expressing reporter TBEV variant.Using this reporter system,we demonstrated that favipiravir possesses antiviral activity against TBEV,with inhibitory concentrations within a pharmacologically relevant range.In conclusion,synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections.The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo,and the derived reporter virus is suitable for antiviral compound screening.展开更多
BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patien...BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patients is under investigation.AIM To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.METHODS We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah,Saudi Arabia.Demographic/clinical data,liver function tests,non-invasive tests for liver fibrosis,and ALBI score/grades were evaluated before and two years after direct-acting antivirals(DAA)treatment.RESULTS The median ALBI score improved from-2.51 to-2.62 after DAA treatment(P<0.05).Additionally,the ALBI score improved irrespective of the level of fibrosis,with improvement more evident in patients with advanced fibrosis(-2.26 to-2.41,P<0.05).The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis(aspartate aminotransferase/alanine aminotransferase ratio,aspartate aminotransferase to platelet ratio index,and fibrosis-4 index)at baseline and after DAA treatment(P<0.05).Moreover,the receiver operating characteristic curve demonstrated ALBI score’s ability to predict advanced fibrosis(F3,F4)[area under the curve=0.76,(95%confidence interval:0.70-0.81),P<0.001,best cut-off value=-2.38(sensitivity 60%and specificity 83%)].CONCLUSION The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA treatment.展开更多
BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients followi...BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.展开更多
Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remain...Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remains limited,we report the isolation and characterization of a novel strain,ECTV-C-Tan-GD01,obtained from rodents in Guangdong Province,China.Nanopore sequencing yielded a complete genome(199 annotated genes,including one gene truncated at the C-terminus)with inverted terminal repeats(ITRs)harboring a conserved hairpin structure.Notably,a frameshift-inducing“G”deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein.In vitro assays demonstrated cell-associated viral replication kinetics,with maximum titers achieved earlier in Vero/HeLa cells(72 h)than in BHK-21/CEF cells(84 h).Murine challenge experiments revealed extreme virulence(LD50<1 plaque-forming unit(PFU)via intranasal/footpad routes)and hepatosplenic tropism.Furthermore,ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures:a single dose of vaccinia virus Tiantan(VTT)or non-replicating vaccinia virus Tiantan(NTV)conferred cross-protection,while tecovirimat(ST-246),cidofovir(CDV),and brincidofovir(initially CMX001)significantly reduced viral loads and pathology.This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.展开更多
Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV ...Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.展开更多
The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspocha...The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.展开更多
TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production ...TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production in ducks are not well understood.Here,we frst found that the polymerase basic 2(PB2)protein of H5N1 subtype AIV inhibited the typeⅠIFN responses by targeting duck mitochondrial antiviral signaling protein(MAVS).We further demonstrated that H5N1-PB2 bound to theΔtransmembrane(ΔTM)domain of duck MAVS,and the polymerase basic 1(PB1)binding domain(PBD)and RNA binding nuclear import domain(RND)of H5N1-PB2 interacted with MAVS to inhibit typeⅠIFN expression in ducks.Collectively,our fndings contribute to understanding the molecular mechanism by which AIV proteins regulate the retinoic acid-inducible geneⅠ(RIG-Ⅰ)-like receptor(RLR)signaling pathway to evade host antiviral immune responses in ducks.展开更多
Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were e...Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were elucidated using comprehensive spectroscopic data,calculated 13C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus(13C NMR-DP4+)probability analysis,and ECD calculations.These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties.Notably,compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane-or rulepidanol-type sesquiterpene,while compound 7 features a hydroxylated monomeric acylphloroglucinol motif.A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus(RSV)with IC50 values ranging from 0.75 to 3.12μmol·L^(-1) compared to the positive control(ribavirin).展开更多
文摘Owing to the emergence of drug resistance and high morbidity,the need for novel antiviral drugs with novel targets is highly sought after.Marine-derived compounds mostly possess potent antiviral activity and serve as a primary source for developing novel antiviral drugs,making the rapid discovery and evaluation of marine antiviral agents particularly crucial.Thus,future research should place greater emphasis on the identification of novel antiviral targets through the combination of artificial intelligence(AI)and structural pharmacology,as well as expanding the marine resource and target databases.
文摘Objective:To evaluate the effectiveness of direct-acting antivirals(DAAs)in patients with chronic hepatitis C,assess changes in liver function and hepatic fibrosis following treatment,and identify independent predictors of treatment failure.Methods:This retrospective cohort study included patients who received DAA therapy at Hospital Kuala Lumpur between January 2020 and December 2023.Sustained virologic response(SVR)was assessed at least 12 weeks post-treatment by reverse transcription-polymerase chain reaction for hepatitis C virus(HCV)RNA.Demographic,clinical,and laboratory data were collected and analyzed.Multiple logistic regression analysis was performed to identify independent predictors of treatment failure.Results:A total of 335 patients in the study.The overall SVR rate was 89%.After achieving SVR,significant improvements were observed in liver enzyme levels and non-invasive liver fibrosis scores,whereas the overall Model for End-Stage Liver Disease(MELD)scores remained unchanged.Significant independent predictors of treatment failure included non-compliance with DAA therapy[adjusted odds ratio(aOR)68.3;95%confidence interval(95%CI)16.3-285.0;P<0.001],treatment with sofosbuvir/velpatasvir(aOR 6.1;95%CI 1.4-26.5;P=0.015),MELD score of 10-15(aOR 4.6;95%CI 1.1-18.2;P=0.031),HCV genotype 3 infection(aOR 4.5;95%CI 1.1-17.6;P=0.031),and elevated serum total bilirubin level(aOR 1.1;95%CI 1.0-1.1;P=0.003).Conclusions:DAA therapy yielded a high SVR rate,and treatment failure was strongly associated with non-adherence to therapy and advanced liver disease.These findings underscore the necessity of adherence support,early diagnosis,and individualized clinical management to optimize treatment outcomes in patients with chronic hepatitis C.
文摘Human knowledge of viruses has experienced explosive growth in the 21st century.This leap forward is reflected not only in the deepening of basic research on viruses but also in addressing public health challenges posed by viral diseases.Key advancements include the rapid identification of emerging viruses and variants,the revelation of diverse viromes and evolutionary patterns,the elucidation of viral pathogenesis-and antiviral targets,as well as development of novel vaccines and antiviral drugs through far more advanced techniques and pipelines(Holmes et al.,2024).Altogether,these breakthroughs are reshaping our understanding of viruses and our strategies to combat viral infections at an unprecedented pace.
基金supported by the National Natural Science Foundation of China(Grant No.:82474195)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:021093002882)+2 种基金the Youth Medical Innovation Research Project of China(Grant No.:P24021887623)Taizhou Science and Technology Support Project,China(Grant No.:TS202420)grants from Nanjing Medical University,China(Grant Nos.:TZKY20230104 and 2024KF0292).
文摘Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
基金supported by the National Key Research and Development Program of China(2022YFC2303300,2023YFC2605504)the National Natural Science Foundation of China(82172273 and 31670165)the Open Research Fund Program of the State Key Laboratory of Virology of China(2023JZZD-01).
文摘Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.
文摘BACKGROUND Sex is one of the known factors influencing the risk of hepatitis C virus(HCV)infection and the natural course of the disease.AIM To evaluate sex-related differences in the characteristics and outcomes of direct-acting antiviral(DAA)treatment in HCV-infected patients.METHODS The study included consecutive 9457 women and 9529 men,treated with DAA for chronic HCV infection from July 2015 to the end of 2023 whose data were collected in the nationwide multicenter retrospective Epiter-2 project.Women were divided into pre-menopausal(15-44 years),menopausal(45-55 years)and post-menopausal(>55 years)and compared with age-matched men.RESULTS Regardless of age,women had a significantly lower body mass index,prevalence of genotype 3 infection and proportion of cirrhosis compared to men.Psychiatric disorders(except depression),hepatitis B virus and human immunodeficiency virus co-infections,as well as alcohol and drug addiction,were significantly less common in women than in men in all age groups.The sustained virologic response was significantly higher in women compared to men in each age group and amounted to 98.4%and 96.6%,respectively(P<0.001).Independent predictors of treatment failure in women were genotype 3 infection,cirrhosis and postmenopausal age.Mild adverse events were reported significantly more often by women,regardless of age with the highest percentage in the postmenopausal group.CONCLUSION DAA treatment is more effective in women than in men,regardless of age,but in postmenopausal women,the effectiveness is relatively the lowest.
基金Supported by the Natural Science Foundation of China,No.81970529the Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mu et al,published in the recent issue of the World Journal of Gastrointestinal Oncology.We pay special attention to the immune tolerance mechanism caused by hepatitis B virus(HBV)infection,the pathogenesis of hepatocellular carcinoma(HCC),and the role of antiviral therapy in treating HCC related to HBV infection.HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways,as well as by inhibiting the immune functions of macrophages,natural killer cells and dendritic cells.In addition,HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8+T cells,ultimately leading to long-term viral infection.The loss of immune cell function caused by HBV infection ultimately leads to HCC.Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
基金financially supported by the National Natural Science Foundation of China(No.22177135)the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-2-006)。
文摘Herein,we report the first asymmetric synthesis of illihenin A,an antiviral sesquiterpenoid bearing a cage-like tricyclo[6.2.2.01,5]dodecane skeleton.Starting from an abundant feedstock(-)-α-cedrene,this19-step synthesis approach features a novel ring-reorganization strategy that includes early stage C7-hydroxylation of the cedrane skeleton and a later-stage ring disassembly-reassembly procedure,affording the desired product with high synthetic efficiency and minimal chiral manipulation.The key transformations include the following:(i)a hydroxy group-directed SmI2-mediated reductive coupling to construct the congested tertiary 7-OH cedrane,(ii)aβ-fragmentation triggered by an alkoxy radical to release a spiro[4.5]decane,and(iii)an intramolecular Aldol reaction,concomitant withα-epimerization,to furnish the tricyclic framework.In addition,preliminary investigation of antiviral activity against CVB3 revealed that illihenin A can significantly inhibit ROS production and apoptosis.
基金supported by the Hubei Agricultural Research System (HBHZDZB-2020-005)the National Natural Science Foundation of China (31872328,32272990)+2 种基金the National Key Research and Development Program of China(2021YFD1800101-2)the Science and Technology Project of Guizhou Province([2020]4Y217)the "Yingzi Tech&Huazhong Agricultural University Intelligent Research Institute of Food Health"(No.IRIFH202209)。
文摘The rapid expansion of large-scale pig farming has brought about a surge in viral diseases with high morbidity rates and diverse manifestations.This widespread occurrence of multiple viral diseases in pig farms has inflicted severe economic losses on the global swine industry.Consequently,there is an urgent need for eco-friendly and efficient antivi-ral drugs that can effectively combat viruses and prevent diseases such as PEDV,PRRSV,PRV,and other viral infections.To this end,we conducted a study on the antiviral activity and cytotoxicity of eleven different Chinese herbal extracts(CHE) against PRV.In vitro testing of several extracts,namely,Echinacea,Ilex purpurea Hassk,Ganoderma lucidum Kars,Taraxacum mongolicum,and Ilex rotunda Thunb,exhibited remarkable inhibition of PRV infection without causing any cytotoxic effects.Specifically,their antiviral selectivity indexes were significantly higher,with values ranging from 6-to 144-fold.The antiviral efficacy of five CHEs was evaluated against other RNA viruses,including PRRSV and PEDV.The extracts showed substantial inhibition of PEDV and PRRSV proliferation.Echinacea and Ilex purpurea Hassk extracts exhibited the highest virus inhibitory effects.To understand the antiviral mechanisms underlying their potent activity,a time-of-addition experiment was conducted.The results indicated that these extracts effectively targeted the early infection and postinfection stages of PRV,PEDV,and PRRSV.The study found that the Chinese herbal extracts,Echinacea and Ilex purpurea Hassk,had both direct and indirect effects on virus particles and cellular targets,demonstrating broad-spectrum antiviral activity against multiple clinical strains of PRV and PEDV.These findings provide a strong foundation for the development of herbal medicines to prevent and treat infections caused by PRV,PEDV and PRRSV in the swine industry.The identified extracts show great promise for the formulation of effective and environmentally friendly antiviral interventions.
文摘BACKGROUND Current antiviral treatment for chronic hepatitis B can suppress viral replication and reduce the risk of cirrhosis and liver cancer.It requires lifelong daily medication,and long-term adherence is often cited as a concern when initiating treatment.Hepatitis B treatment adherence in the context of the patient’s medical and life experiences remains underexplored.AIM To evaluate factors associated with adherence to hepatitis B oral antiviral treatment.METHODS A global online survey was administered anonymously to adults(aged 18 years or older)living with chronic hepatitis B.A subsample of 614 individuals who reported being on hepatitis B treatment was included in the analysis.Indices for treatment affordability,healthcare service acceptability,and individual physical,psychological,and emotional functioning were constructed(Cronbach’s alpha=0.71-0.83).Data analysis was conducted using Stata/BE 17.0.RESULTS Overall,81%of respondents reported high adherence to hepatitis B treatment.Lower adherence was observed among individuals who identified as African or African American(P=0.008).Among participants with low adherence,60%cited affordability as a challenge(P=0.068),53%identified healthcare service acceptability as a challenge(P=0.04),79%described physical functioning as a challenge(P=0.002),and 40.5%reported difficulties with psychological functioning(P=0.55).CONCLUSION Findings demonstrate high treatment adherence,although access to and acceptability of healthcare services,as well as an individual’s physical functioning challenges,appear to be related to low adherence.
文摘Sickle cell disease(SCD)is a genetic disorder that predisposes affected individuals to a range of complications,including an increased susceptibility to viral infections.These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients.This review examines the interaction between viral infections and SCD,highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population.Advances in antiviral therapies have significantly improved outcomes,yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions,altered pharmacokinetics,and the potential exacerbation of SCDrelated complications.Additionally,vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention.By focusing on both established and novel antiviral treatments,this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.
文摘Objective To estimate the antiviral activities of ulvan derived from Ulva pertusa,and initiate a preliminary exploration into its mechanism for the potential utilization of ulvans in the future.Methods Employing methodologies rooted in molecular biology and virology,such as viral infection and FACS,the effect of ulvan on virus infection and the innate immune responses in cells were evaluated.Results Ulvan significantly restricted vesicular stomatitis virus(VSV)infection.Preliminary exploration on its mechanism indicated that ulvan activated the innate immune,and induced type I interferons(IFN-Ⅰ)expression to restrict viral infection.
基金supported by funds from the scientific and technical program BR218004/0223“Improving measures to ensure biological safety in Kazakhstan:counteracting dangerous and especially dangerous infections”.Part of this work carried out in Russian Federation was supported by internal grant funding from the Scientific Centre for Family Health and Human Reproduction Problems:grant number 121022500179-0.Title:“Molecular,Organismal,and Population Patterns of the Epidemic Process of Anthropozoonotic and Transmissible Infections in the Territory of Northern Asia and Adjacent Areas”.
文摘Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines.However,the absence of reference TBEV strains in the country presented a major challenge.To address this,we generated a prototype strain(Vasilchenko)of the Siberian TBEV genotype,predominant in Kazakhstan,using synthetic genome and molecular infectious clone technology.A DNA-launched TBEV molecular clone was assembled from DNA fragments,enabling virus rescue upon plasmid transfection.During the propagation of the post-transfection virus in cell culture,a single amino acid substitution(E51K)in the envelope protein emerged,resulting in a 100-fold increase in the titer of the mutant variant.In vivo,this mutation significantly attenuated virulence:while wild-type TBEV caused 100%mortality in BALB/c mice,the E51K variant was non-lethal and exhibited reduced viremia,suggesting impaired neuroinvasiveness.To further exploit this attenuated,high-titer virus,we developed a GFP-expressing reporter TBEV variant.Using this reporter system,we demonstrated that favipiravir possesses antiviral activity against TBEV,with inhibitory concentrations within a pharmacologically relevant range.In conclusion,synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections.The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo,and the derived reporter virus is suitable for antiviral compound screening.
文摘BACKGROUND The albumin-bilirubin(ALBI)score was developed as a prognostic tool for pa-tients with hepatocellular carcinoma.However,its new role as an indicator of liver fibrosis in chronic hepatitis C virus(HCV)patients is under investigation.AIM To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.METHODS We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah,Saudi Arabia.Demographic/clinical data,liver function tests,non-invasive tests for liver fibrosis,and ALBI score/grades were evaluated before and two years after direct-acting antivirals(DAA)treatment.RESULTS The median ALBI score improved from-2.51 to-2.62 after DAA treatment(P<0.05).Additionally,the ALBI score improved irrespective of the level of fibrosis,with improvement more evident in patients with advanced fibrosis(-2.26 to-2.41,P<0.05).The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis(aspartate aminotransferase/alanine aminotransferase ratio,aspartate aminotransferase to platelet ratio index,and fibrosis-4 index)at baseline and after DAA treatment(P<0.05).Moreover,the receiver operating characteristic curve demonstrated ALBI score’s ability to predict advanced fibrosis(F3,F4)[area under the curve=0.76,(95%confidence interval:0.70-0.81),P<0.001,best cut-off value=-2.38(sensitivity 60%and specificity 83%)].CONCLUSION The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA treatment.
文摘BACKGROUND Liver function of chronic hepatitis B(CHB)patients is essentially normal after treatment with antiviral drugs.In rare cases,persistently abnormally elevatedα-fetoprotein(AFP)is seen in CHB patients following long-term antiviral treatment.However,in the absence of imaging evidence of liver cancer,a reasonable expla-nation for this phenomenon is still lacking.AIM To explore the causes of abnormal AFP in patients with CHB who were not diag-nosed with liver cancer.METHODS From November 2019 to May 2023,15 patients with CHB after antiviral treatment and elevated AFP were selected.Clinical data and quality indicators related to laboratory testing,imaging data,and pathological data were obtained through inpatient medical records.RESULTS All patients had increased AFP and significantly elevated IgG.Cancer was excluded by imaging examination.Only four patients had elevated alanine ami-notransferase,10 had elevated aspartate aminotransferase,nine had elevated total bilirubin,and two had antinuclear antibodies.The liver biopsy and histopatho-logical examination indicated that 14 patients had rosette,moderate,or higher interfacial inflammation,lymphocyte infiltration,and severe hepatic fibers(11 cases),which was consistent with the pathological features of autoimmune hepa-titis(AIH).After 8-12 week of hormone therapy,the levels of AFP and IgG,and liver function returned to normal(P<0.05).CONCLUSION For patients with CHB and elevated AFP after antiviral treatment,autoimmune hepatitis should be considered.CHB with AIH is clinically insidious and difficult to detect,and prone to progression to cirrhosis.Liver puncture pathological examination should be performed when necessary to confirm diagnosis.
基金supported by the Natural Science Foundation of Beijing(7254390)the Youth Science Foundation of Chinese Center for Disease Control and Prevention(2024A103)to W.C.C,the National Key ResearchDevelopment Program of China(2022YFC2304100,2023YFD1800405).
文摘Ectromelia virus(ECTV),a member of the Orthopoxvirus genus,serves as both a causative agent of mousepox and a pivotal surrogate model for studying highly pathogenic orthopoxviruses.Although genomic data on ECTV remains limited,we report the isolation and characterization of a novel strain,ECTV-C-Tan-GD01,obtained from rodents in Guangdong Province,China.Nanopore sequencing yielded a complete genome(199 annotated genes,including one gene truncated at the C-terminus)with inverted terminal repeats(ITRs)harboring a conserved hairpin structure.Notably,a frameshift-inducing“G”deletion in the EV159 gene resulted in the truncation of a semaphorin-like protein.In vitro assays demonstrated cell-associated viral replication kinetics,with maximum titers achieved earlier in Vero/HeLa cells(72 h)than in BHK-21/CEF cells(84 h).Murine challenge experiments revealed extreme virulence(LD50<1 plaque-forming unit(PFU)via intranasal/footpad routes)and hepatosplenic tropism.Furthermore,ECTV-C-Tan-GD01 exhibited utility in evaluating orthopoxvirus countermeasures:a single dose of vaccinia virus Tiantan(VTT)or non-replicating vaccinia virus Tiantan(NTV)conferred cross-protection,while tecovirimat(ST-246),cidofovir(CDV),and brincidofovir(initially CMX001)significantly reduced viral loads and pathology.This study establishes ECTV-C-Tan-GD01 as a dual-purpose resource for probing orthopoxvirus evolution and advancing therapeutic development.
基金funded by National Natural Science Foundation of China(92578123)Shenzhen High-level Hospital Construction Fund(23250G1001)+3 种基金the Sanming Project of Medicine in Shenzhen(SZSM202311033)National Key Research and Development Program of China(2023YFC2606004)National Natural Science Foundation of China(32501262)Beijing Institute of Technology Research Fund Program for Young Scholars(6120220072).
文摘Dengue virus(DENV)is a mosquito-borne pathogen responsible for a spectrum of illnesses,including dengue fever,dengue hemorrhagic fever,and dengue shock syndrome.Nearly half of the global population is at risk of DENV infection,making it a pressing public health issue worldwide.The limited cross-protection among the four DENV serotypes(DENV1-4)and the phenomenon of antibody-dependent enhancement(ADE)have posed significant challenges to the development of effective dengue vaccines.Furthermore,there are currently no specific antiviral treatments available.This review provides an overview of DENV's key characteristics,clinical manifestations,and recent advancements in antiviral drug development-including the repurposing of approved drugs,peptidebased antiviral agents,therapeutic antibodies,natural products with antiviral potential,and host factor inhibitors-aiming to offer critical insights to inform strategies for managing and preventing dengue outbreaks.
基金supported by the National Natural Science Foundation of China(Nos.31972852,32371496,and 81903527)the Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302)。
文摘The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery.In this study,by screening fungal extracts against coxsackievirus B3(CVB3),three new aspochalasins,templichalasins A-C(1-3),along with six known aspochalasins(4-9)were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045.Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system,while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons.Their structures were characterized through extensive spectroscopic analyses,electronic circular dichroism(ECD)calculations,and single-crystal X-ray diffraction analysis.Additionally,we demonstrated that compound 4 can be readily converted into compounds 1-3 under mild acidic conditions and proposed a plausible mechanism for this conversion.Bioactivity evaluation of compounds 1-9 against CVB3 revealed the inhibitory effects of all compounds against the virus.Notably,compound 9 exhibited superior antiviral activity,surpassing the commercial drug ribavirin in selectivity index(SI)value.
基金supported by the grants from the National Natural Science Foundation of China(31872497 and 32072844)the National Key Research and Development Program of China(2021YFD1800200 and 2016YFD0500207)the Laboratory of Lingnan Modern Agriculture Project,China(NT2021007)。
文摘TypeⅠinterferon(IFN)-mediated innate immune responses represent the first line of host defense against viral infection.However,the molecular mechanisms by which avian infuenza virus(AIV)inhibits typeⅠIFN production in ducks are not well understood.Here,we frst found that the polymerase basic 2(PB2)protein of H5N1 subtype AIV inhibited the typeⅠIFN responses by targeting duck mitochondrial antiviral signaling protein(MAVS).We further demonstrated that H5N1-PB2 bound to theΔtransmembrane(ΔTM)domain of duck MAVS,and the polymerase basic 1(PB1)binding domain(PBD)and RNA binding nuclear import domain(RND)of H5N1-PB2 interacted with MAVS to inhibit typeⅠIFN expression in ducks.Collectively,our fndings contribute to understanding the molecular mechanism by which AIV proteins regulate the retinoic acid-inducible geneⅠ(RIG-Ⅰ)-like receptor(RLR)signaling pathway to evade host antiviral immune responses in ducks.
基金supported by the National Natural Science Foundation of China(Nos.82173695,82003609 and 82003743)the Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515011896 and 2020A1515110453)+1 种基金the Science and Technology Planning Project of Guangzhou City(No.2023A03J0566)the High-performance Public Computing Service Platform of Jinan University.
文摘Seven novel acylphloroglucinol-sesquiterpenoid adducts,designated as dryatraols J-P(1-7),were isolated from the rhizomes of Dryopteris atrata(Wall.ex Kunze)Ching.The structures,including absolute configurations,were elucidated using comprehensive spectroscopic data,calculated 13C Nuclear Magnetic Resonance-Diastereotopic Probability Assignment Plus(13C NMR-DP4+)probability analysis,and ECD calculations.These structures represent a rare subclass of carbon skeleton of acylphloroglucinol-sesquiterpenoid adducts with a furan ring connecting the acylphloroglucinol and sesquiterpenoid moieties.Notably,compounds 1-6 are the first reported examples of acylphloroglucinol-sesquiterpenoid adducts with dimeric acylphloroglucinol incorporated into the aristolane-or rulepidanol-type sesquiterpene,while compound 7 features a hydroxylated monomeric acylphloroglucinol motif.A preliminary evaluation of their antiviral activities revealed that compounds 1-6 exhibited more potent activities against respiratory syncytial virus(RSV)with IC50 values ranging from 0.75 to 3.12μmol·L^(-1) compared to the positive control(ribavirin).
