Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytia...Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.展开更多
[Objective] To investigate the mechanism of compound traditional Chinese medicine （TCM） on Newcastle disease virus （NDV） and to provide a scientific basis for the reasonable usage of antiviral drugs in clinic. [Me...[Objective] To investigate the mechanism of compound traditional Chinese medicine （TCM） on Newcastle disease virus （NDV） and to provide a scientific basis for the reasonable usage of antiviral drugs in clinic. [Method] The compound TCM was composed of Hedyotis diffusa, Lonicera japonica Thunb, Radix astragali and Glycyrrhiza uralensis. Different dilutions of fluid extract were prepared. Its antiviral effects on NDV were observed through three inoculation ways, first, inoculation with the medicine and NDV mixture which had been incubated at 37 ℃; second, incubating chicken embryo fibroblasts （CEF） with the medicine followed by inoculation with NDV; third, inoculation with N DV followed by incubating CEF with the medicine. The A,= was determined by M]-r [ 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） ~ method. Therapeutic indexes were used to evaluate the antiviral effects. [ Result] The minimum effective concentration of the compound TCM which acted through the three ways was 1.0 × 2^-10 1.0 × 2^-8 and 1.0 × 2^-7 g/ml, respectively. The antiviral effects of the compound TCM were the best through inoculation with the incubated medicine and NDV mixture, followed by the second method and the third method. [ Conclusion] The compound TCM can not only kill NDV directly in vitro but also inhibit viral propagation.展开更多
Natural product-based antiviral candidates have received significant attention.However,there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance.Baicalein and ...Natural product-based antiviral candidates have received significant attention.However,there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance.Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi.They have proven to be effective against a broad range of viruses by directly killing virus particles,protecting infected cells,and targeting viral antigens on their surface,among other mechanisms.As natural products,they both possess the advantage of lower toxicity,enhanced therapeutic efficacy,and even antagonistic effects against drug-resistant viral strains.Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds,demonstrating their antiviral properties.However,to date,no review on the antiviral effects of baicalein and baicalin has been published.This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms.The aim is to provide a basis for the rational development and utilization of baicalein and baicalin,as well as to promote antiviral drug research.展开更多
Spring viremia of carp virus(SVCV)is globally widespread and poses a serious threat to aquatic ecology and aquaculture due to its broad host range.To develop effective agents to control SVCV infection,we selected 16 n...Spring viremia of carp virus(SVCV)is globally widespread and poses a serious threat to aquatic ecology and aquaculture due to its broad host range.To develop effective agents to control SVCV infection,we selected 16 naturally active small molecules to assess their anti-SVCV activity.Notably,dihydroartemisinin(DHA)(100μmol/L)and(S,S)-(+)-tetrandrine(TET)(16μmol/L)exhibited high antiviral effects in epithelioma papulosum cyprinid(EPC)cells,with inhibitory rates of 70.11%and 73.54%,respectively.The possible antiviral mechanisms were determined as follows:1.Preincubation with DHA and TET decreased viral particle infectivity in fish cells,suggesting that horizontal transmission of SVCV in the aquatic environment was disrupted;2.Although neither had an effect on viral adhesion,TET(but not DHA)interfered with SVCV entry into host cells(>80%),suggesting that TET may have an antiviral function in early viral replication.For in vivo study,both agents enhanced the survival rate of SVCV-infected zebrafish by 53.3%,significantly decreased viral load,and modulated the expression of antiviralrelated genes,indicating that DHA and TET may stimulate the host innate immune response to prevent viral infection.Overall,our findings indicated that DHA and TET had positive effects on suppressing SVCV infection by affecting early-stage viral replication,thus holding great potential as immunostimulants to reduce the risk of aquatic rhabdovirus disease outbreaks.展开更多
Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of v...Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of virus. The early stage of infection is the stage ofinteraction between the virus and the host's defence system. Once the latter is breached, the earlynon-specific or innate immune components such as interferon (IFN), natural killer (NK) cells andmacrophages become active. As the infection proceeds, the adaptive (specific) immune responsedevelops, with the appearance of cytotoxic T cells, helper T cells and antiviral antibodies.Antibodies provide a major barrier to virus spread between cells and cells and are particularlyimportant in restriction of virus spread in the blood stream. Virus infection directly activates thetranscription of type Ⅰ IFN (IFN-alfa/beta) genes in infected cells, while the type Ⅱ IFN(IFN-gamma) plays an essential role in the regulation of an adaptive immune response rather thaninnate immune response. Therefore, Type Ⅰ IFN is the first defence for host and neighbouring cellsto resist virus infection.展开更多
The COVID-19 pandemic has exposed the limitations of traditional preventative measures and underscored the essential role of face masks in controlling virus transmission.More effective and recyclable facial masks usin...The COVID-19 pandemic has exposed the limitations of traditional preventative measures and underscored the essential role of face masks in controlling virus transmission.More effective and recyclable facial masks using various materials have been developed.In this work,vertically aligned carbon nanotubes(VACNTs)are employed as effective facial mask filters,particularly aimed at preventing SARS-CoV-2 virus infection in preparation for future COVID-19 pandemics.This study assesses six critical aspects of facial masks:hydrophobicity,industrial viability,breathability,hyperthermal antiviral effect,toxicity,and reusability.The VACNT alone exhibits superhydrophobicity with a contact angle of 175.53◦,and an average of 142.7◦for a large area on spun-bonded polypropylene.VACNTs are processed using a roll-to-roll method,eliminating the need for adhesives.Due to the aligned tubes,VACNT filters demonstrate exceptional breathability and moisture ventilation compared to previously reported CNT and conventional filters.Hyperthermal tests of VACNT filters under sunlight confirm that up to 99.8%of the HCoV 229E virus denatures even in cold environments.The safety of using VACNTs is corroborated through histopathological evaluation and subcutaneous implantation tests,addressing concerns of respiratory and skin inflammation.VACNT masks efficiently transmit moisture and rapidly return to their initial dry state under sunlight maintaining their properties after 10000 bending cycles.In addition,the unique capability of VACNT filters to function as respiratory sensors,signaling dampness and facilitating reuse,is assessed,alongside their Joule heating effect.展开更多
Objective：To explore the potential effects of berberine on influenza virus infection both in vitro and in vivo.Methods：In vitro anti-influenza virus assays were performed by cytopathogenic effect and neuraminidase a...Objective：To explore the potential effects of berberine on influenza virus infection both in vitro and in vivo.Methods：In vitro anti-influenza virus assays were performed by cytopathogenic effect and neuraminidase assays in Madin Darby canine kidney cells.In vivo anti-influenza virus assays were performed on the viral pneumonia model of mice.The numbers of mice that died within day 2 to day 14 postinfection were recorded to calculate the mortality.On days 2,4,and 6,the viral titers in the lungs were determined by hemagglutination assay;hematoxylin/eosin staining was used to assess the pathogenic changes of lung tissues; the concentrations of tumor necrosis factor-alpha（TNF-α） and monocyte specific chemoattractant molecule （MCP-1） were measured by radio immunoassay or enzyme-linked immunosorbent assay;the concentrations of nitric oxide（NO） and inducible nitric oxide synthetase（iNOS） were detected by colorimetric method;reverse transcription polymerase chain reaction was used to detect the mRNA level of TNF-αand MCP-1.Results： Berberine showed inhibitory effects on cytopathogenic effects and neuraminidase activity of virus,with the therapeutic index 9.69.In vivo,berberine decreased mice mortality from 90%to 55%,reduced virus titers in the lungs on day 2 postinfection（P0.05）.The lung histology scores were 1.50±0.67,4.50±1.00,and 5.50±1.00 in the berberine group on days 2,4,and 6,respectively,which were significantly reduced compared to 2.17±0.22,6.83±0.44,and 8.50±0.33 in the infected group（P0.05）.The productions of NO and iNOS were repressed by berberine compared with those in the infected group（P0.01）.The transcription and expression of TNF-αwere inhibited by berberine on day 4（P0.01） and day 6（P0.05）,and those of MCP-1 were inhibited on day 6（P0.01） compared with the infected group.Conclusions：Berberine exhibited antiviral effects on the influenza virus both in vitro and in vivo.The possible therapeutic mechanism of berberine on influenza-induced viral pneumonia might be inhibiting the virus infection,as well as improving the pathogenic changes by repressing inflammatory substances release展开更多
Engineering complex nanocomposites that specifically target the hepatitis B virus （HBV） and overcome the limitations of current therapies such as limited efficacy and serious side effects is very challenging. Here, ...Engineering complex nanocomposites that specifically target the hepatitis B virus （HBV） and overcome the limitations of current therapies such as limited efficacy and serious side effects is very challenging. Here, for the first time, the antiviral effect of engineered plasmonic gold and layered double hydroxide self-assemblies （AuNPs/LDHs） is demonstrated, using HBV as a model virus and hepatoma-derived HepG2.2.215 ceils for viral replication, assembly, and secretion of infectious virions and subviral particles. AuNPs/LDHs were obtained by a simple, cost-effective procedure in which small AuNPs （-3.5 nm） were directly obtained and organized on the surface of larger LDH nanoparticles （-150 nm） by exploiting the capability of MgLDH, ZnLDH, and MgFeLDH to manifest their ＂structural memory＂ in the aqueous solution of Au（O2CCH3）3. The self-assembly approach of AuNPs and LDHs was assessed by transmission electron microscopy （TEM）, X-ray photoelectron spectroscopy （XPS）, powder X-ray diffraction （PXRD）, and UV-Vis analysis （UV-Vis）. All AuNPs/LDHs tested reduced the amount of viral and subviral particles released from treated cells by up to 80% and exhibited good cytocompatibility. AuNPs/MgFeLDH showed the highest antiviral HBV response with more than 90% inhibition of HBV secretion for the whole concentration range. Preliminary studies on the mechanism of HBV inhibition reveals that in the presence of AuNPs/LDHs, HBV particles are sequestered within the treated cells. The antiviral and low cytotoxic plasmonic properties of these Au/LDH nanocomposites indicate that they hold significant potential to be tailored as novel efficient therapeutics for the treatment of hepatitis B.展开更多
Oligodeoxynucleotides (Oligomers) including modified and unmodified, homo-and heterooligomers were tested for their ability to inhibit mouse SRS leukemia virus (SRSV)-induced proliferation of cells, colony formation, ...Oligodeoxynucleotides (Oligomers) including modified and unmodified, homo-and heterooligomers were tested for their ability to inhibit mouse SRS leukemia virus (SRSV)-induced proliferation of cells, colony formation, syncytium formation and reverse transcriptase (RT) activity in vitro. Phosphorothioate analogs complementary to Mo-MuLV sequences, as well as noncomplementary homooligomers, were found to be active. Unmodified homooligomer (dC14) also showed inhibition of growth of ascitic lymphoma carrying SRS virus. Our study suggests that different classes of oligonucleotides may inhibit SRSV replication with different mechanisms.展开更多
Turmeric is an herbal plant that is widely used as a traditional herbal medicine in many countries. Curcumin displays its anti-viral activities through several mechanisms of action. In this case report we present a 10...Turmeric is an herbal plant that is widely used as a traditional herbal medicine in many countries. Curcumin displays its anti-viral activities through several mechanisms of action. In this case report we present a 10-year-old child with herpetic vesiculo-ulcerative lesions who was treated with turmeric along with systemic acyclovir which resulted in complete healing by the third day of application.展开更多
Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been s...Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19.The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2.The Web of Science,PubMed,Scopus,and Google Scholar were searched using keywords:“COVID-19”,“SARS-CoV-2”,“Kaempferol”and“Quercetin”in the Title/Abstract.Relevant published articles in the English language until August 2020 were considered.Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel(3a channel)expressed in SARS-CoV infected cells.They also reduced the level of reactive oxygen species,expression of inducible nitric oxide synthase,pro-inflammatory mediators including TNF-α,IL-1α,IL-1β,IL-6,IL-10,and IL-12 p70,and chemokines.Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral,antioxidant,anti-inflammatory,and immunomodulatory effects.展开更多
Propolis is a natural substance made from resins collected from trees and plants, and which bees combine with pollen, wax, and their own enzymes. It has a complex chemical composition that varies with the harvest seas...Propolis is a natural substance made from resins collected from trees and plants, and which bees combine with pollen, wax, and their own enzymes. It has a complex chemical composition that varies with the harvest season, vegetation type, bee species, and geographical region. Thanks to its components, it has valuable biological properties such as antifungal, antibacterial, anticancer, antiviral, and immunomodulatory activity. For this study, a sample of propolis harvested in April 2019 was used, which came from a bee native to Mexico (<span style="white-space:nowrap;"><i>Plebeia frontalis</i></span>) in whose geographical environment there are seven other native species. Canine distemper virus is an RNA virus that causes a systemic infection with high fatality rates in vips without protective immunity. In this work, the antiviral effect of <span style="white-space:nowrap;"><i>Plebeia frontalis</i></span> propolis on canine distemper virus was tested, administering it one hour before and simultaneously to infection. The antiviral effect was evaluated by determining cellular viability with the MTT assay. The results obtained show that this propolis has a statistically significant antiviral effect on both treatments, although it is slightly better when applied one hour before viral infection, so we can recommend it as an antiviral treatment in both domestic animals and human beings. There are currently few studies of the antiviral effect of propolis, this being the first study of a melliponium propolis in veterinary medicine.展开更多
Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-g...Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-genome system was used to screen drugs with inhibitory effect on SFTSV replication and transcription,and the 50%inhibitory concentration(IC_(50))of each drug was calculated by drug concentration gradient inhibition experiment.Drugs were used to pre-incubate with virus and then incubate with cells,to incubate with virus and cells simultaneously,to incubate with cells after virus invading into cells,or to incubate during the whole infection process,and then qRT-PCR was used to measure the viral RNA copies in the culture supernatant.These experiments were performed to quantitatively determine the inhibition effects of drugs on SFTSV indifferent stages of the whole process including virion stability,entry and post-entry stages,so as to clarify the inhibition mechanism of these drugs.Results:Four drugs including Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide,and Vidofludimus were identified having efficient inhibitory effects on SFTSV RNA replication via minigenome system,with the IC_(50) of 0.014μmol/L,0.627μmol/L,1.283μmol/L,and 0.059μmol/L,respectively.All four drugs showed effective inhibition when adding during the whole SFTSV infection process as well as the post-entry stage.Conclusion:Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide and Vidofludimus show efficient anti-viral effects on SFTSV infection.展开更多
Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea offici...Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.展开更多
Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter ...Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter to get solution. Cyclopiazonic acid(CPA)was used as positive control. The toxicity of Guanhuang Ganmao Keli on Hep-2 cells was tested by cell counting kit 8(CCK-8). The protective effect of Guanhuang Ganmao Keli on RSV was evaluated under the highest toxic concentration. Results:The TC50 and EC50 of Guanhuang Ganmao Keli is 0.647 mg/mL and 0.014 mg/mL,respectively. Guanhuang Ganmao Keli showed significant antiviral effect when added 0、2、4、6 and 8 h post-infection. Conclusion:Guanhuang Ganmao Keli is an effective antiviral agent on RSV in vitro.展开更多
[Objectives]To study the toxic effect and antiviral activity of anthraquinone extract of Polygonum cuspidatum on infection of Koi herpes virus(KHV).[Methods]The MTT method and CPE microscopy were used to detect the co...[Objectives]To study the toxic effect and antiviral activity of anthraquinone extract of Polygonum cuspidatum on infection of Koi herpes virus(KHV).[Methods]The MTT method and CPE microscopy were used to detect the common carp brain(CCB)cytotoxicity of the P.cuspidatum anthraquinone extract in 48 h.Eight groups of different concentrations of the P.cuspidatum anthraquinone extract 1.96,3.91,7.28,15.63,31.25,62.5,125,250μg/mL experimental groups and a control group without drug effect were set up.After determining the maximum non-toxic range of the P.cuspidatum anthraquinone extract,the viral replication inhibition test was carried out.[Results]The concentration of the P.cuspidatum anthraquinone extract 31.25μg/mL was recognized as the maximum non-toxic concentration.The survival rate of CCB cells was higher than 80%,and the toxic dose(CC50)of the drug for 50%cell death was(72.67±2.12)μg/mL.The maximum inhibition rate of the P.cuspidatum anthraquinone extract was 78.63%±5.47%at a concentration of 31.25μg/mL,and the 50%effective drug dose(IC50)for inhibiting the virus was(13.67±0.47)μg/mL,and the therapeutic index(TI)was 5.48±0.49.In the direct virus killing test,the highest virus inhibition rate was 32.21%.[Conclusions]Under the experimental conditions,it can be concluded that the P.cuspidatum anthraquinone extract has high anti-KHV activity,and at the same time.It is expected to lay a theoretical foundation for the research of P.cuspidatum anthraquinone extract against KHV.展开更多
Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine deriva...Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.展开更多
African swine fever virus(ASFV)is an important pathogen that causes a highly contagious and lethal disease in swine,for which neither a vaccine nor treatment is available.The DNA repair enzyme 8-oxoguanine DNA glycosy...African swine fever virus(ASFV)is an important pathogen that causes a highly contagious and lethal disease in swine,for which neither a vaccine nor treatment is available.The DNA repair enzyme 8-oxoguanine DNA glycosylase 1(OGG1),which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine(8-oxoG),has been linked to the pathogenesis of different diseases associated with viral infections.However,the role of OGG1-base excision repair(BER)in ASFV infection has been poorly investigated.Our study aimed to characterize the alteration of host reactive oxygen species(ROS)and OGG1 and to analyse the role of OGG1 in ASFV infection.We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1.Viral yield,transcription level,and protein synthesis were reduced in ASFV-infected primary alveolar macrophages(PAMs)treated by TH5487 or SU0268 inhibiting OGG1.The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs.Furthermore,OGG1 was found to negatively regulate interferonβ(IFN-β)production during ASFV infection and IFN-βcould be activated by OGG1 inhibition with TH5487 and SU0268,which blocked OGG1 binding to 8-oxoG.Additionally,the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-βproduction to further affect ASFV replication.These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.展开更多
Coronavirus disease 2019(COVID-19)infection is unequivocally the worst crisis in recent decades,which is caused by a severe acute respiratory virus 2.Currently,there is no effective therapy for the COVID-19 infection....Coronavirus disease 2019(COVID-19)infection is unequivocally the worst crisis in recent decades,which is caused by a severe acute respiratory virus 2.Currently,there is no effective therapy for the COVID-19 infection.Different countries have different guidelines for treating COVID-19 in the absence of an approved therapy for COVID-19.Therefore,there is an imminent need to identify effective treatments,and several clinical trials have been conducted worldwide.Both hydroxychloroquine[HCQS],chloroquine,and azithromycin(AZ)have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 virus.However,there is evidence both in favor and against the use of hydroxychloroquine and azithromycin(HCQS+AZ)combination therapy to manage the COVID-19 infection.The combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse events.However,the inference of these findings was from observational studies.Therefore,large randomized trials are imperative to show the future path for the use of HCQS+AZ combination therapy.However,owing to the ban on HCQS use in COVID-19,this may no longer be essential.This review is on the pharmacology,trials,regimens,and side effects of hydroxychloroquine and azithromycin combination therapy.展开更多
The world is witnessing seismic shifts in the landscape of liver disease aetiologies encountered in clinical practice.In part,this is due to effective antiviral therapeutics complimented by sound public health policy,...The world is witnessing seismic shifts in the landscape of liver disease aetiologies encountered in clinical practice.In part,this is due to effective antiviral therapeutics complimented by sound public health policy,the combination of which has been highly successful in controlling hepatitis B and in reducing the burden of chronic hepatitis C.Unfortunately,economic prosperity,rising living standards and changes in dietary patterns and physical activity have heralded a new era of liver diseases defined by rising rates of metabolic syndrome and consequent metabolic dysfunction associated fatty liver disease(MAFLD).展开更多
基金supported by grants from the National Mega Project on Major Drug Development(No.2009ZX09301-014-1)National Natural Science Foundation of China(No.81371865)
文摘Summary： Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus （CV） and respira- tory syncytial virus （RSV）. However, no antiviral agents with low toxicity and drug resistance are cur- rently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin （an ingredient of Rheum palmatum） against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum pal- matum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication in- hibition, virucidal and anti-absorption effects, by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tet- razolium bromide （MTT） assay and plaque reduction assay （PRA）. The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR （qPCR）. Cytokine （IFN-γ, TNF-α） mRNA expressions after emodin treatment （7.5, 15, 30 μmol/L） were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration （EC50） ranging from 13.06 to 14.27 μmol/L and selectivity index （SI） being 5.38-6.41 μmol/L. However, emodin couldn＇t directly inacti- vate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.
文摘[Objective] To investigate the mechanism of compound traditional Chinese medicine （TCM） on Newcastle disease virus （NDV） and to provide a scientific basis for the reasonable usage of antiviral drugs in clinic. [Method] The compound TCM was composed of Hedyotis diffusa, Lonicera japonica Thunb, Radix astragali and Glycyrrhiza uralensis. Different dilutions of fluid extract were prepared. Its antiviral effects on NDV were observed through three inoculation ways, first, inoculation with the medicine and NDV mixture which had been incubated at 37 ℃; second, incubating chicken embryo fibroblasts （CEF） with the medicine followed by inoculation with NDV; third, inoculation with N DV followed by incubating CEF with the medicine. The A,= was determined by M]-r [ 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） ~ method. Therapeutic indexes were used to evaluate the antiviral effects. [ Result] The minimum effective concentration of the compound TCM which acted through the three ways was 1.0 × 2^-10 1.0 × 2^-8 and 1.0 × 2^-7 g/ml, respectively. The antiviral effects of the compound TCM were the best through inoculation with the incubated medicine and NDV mixture, followed by the second method and the third method. [ Conclusion] The compound TCM can not only kill NDV directly in vitro but also inhibit viral propagation.
基金supported by National Natural Science Foundation of China(No.81573585)the Innovative Practice of Undergraduate Project of Naval Medical University(No.FH2021104)。
文摘Natural product-based antiviral candidates have received significant attention.However,there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance.Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi.They have proven to be effective against a broad range of viruses by directly killing virus particles,protecting infected cells,and targeting viral antigens on their surface,among other mechanisms.As natural products,they both possess the advantage of lower toxicity,enhanced therapeutic efficacy,and even antagonistic effects against drug-resistant viral strains.Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds,demonstrating their antiviral properties.However,to date,no review on the antiviral effects of baicalein and baicalin has been published.This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms.The aim is to provide a basis for the rational development and utilization of baicalein and baicalin,as well as to promote antiviral drug research.
基金supported by the National Natural Science Foundation of China(31902410)Natural Science Foundation of Zhejiang Province(LQ22C190002)+3 种基金Natural Science Foundation of Ningbo City(2021J117)Program of Science and Technology Department of Ningbo City(2021S058)One Health Interdisciplinary Research Project of Ningbo University(HZ202201)Zhejiang Xinmiao Talents Programs(2022R405B066)。
文摘Spring viremia of carp virus(SVCV)is globally widespread and poses a serious threat to aquatic ecology and aquaculture due to its broad host range.To develop effective agents to control SVCV infection,we selected 16 naturally active small molecules to assess their anti-SVCV activity.Notably,dihydroartemisinin(DHA)(100μmol/L)and(S,S)-(+)-tetrandrine(TET)(16μmol/L)exhibited high antiviral effects in epithelioma papulosum cyprinid(EPC)cells,with inhibitory rates of 70.11%and 73.54%,respectively.The possible antiviral mechanisms were determined as follows:1.Preincubation with DHA and TET decreased viral particle infectivity in fish cells,suggesting that horizontal transmission of SVCV in the aquatic environment was disrupted;2.Although neither had an effect on viral adhesion,TET(but not DHA)interfered with SVCV entry into host cells(>80%),suggesting that TET may have an antiviral function in early viral replication.For in vivo study,both agents enhanced the survival rate of SVCV-infected zebrafish by 53.3%,significantly decreased viral load,and modulated the expression of antiviralrelated genes,indicating that DHA and TET may stimulate the host innate immune response to prevent viral infection.Overall,our findings indicated that DHA and TET had positive effects on suppressing SVCV infection by affecting early-stage viral replication,thus holding great potential as immunostimulants to reduce the risk of aquatic rhabdovirus disease outbreaks.
文摘Viruses are obligatory intracellular parasites. Most of the cells in animaland human body possess the innate ability to fight viruses. Innate immune function restrictsinfection at the early stage and delay spread of virus. The early stage of infection is the stage ofinteraction between the virus and the host's defence system. Once the latter is breached, the earlynon-specific or innate immune components such as interferon (IFN), natural killer (NK) cells andmacrophages become active. As the infection proceeds, the adaptive (specific) immune responsedevelops, with the appearance of cytotoxic T cells, helper T cells and antiviral antibodies.Antibodies provide a major barrier to virus spread between cells and cells and are particularlyimportant in restriction of virus spread in the blood stream. Virus infection directly activates thetranscription of type Ⅰ IFN (IFN-alfa/beta) genes in infected cells, while the type Ⅱ IFN(IFN-gamma) plays an essential role in the regulation of an adaptive immune response rather thaninnate immune response. Therefore, Type Ⅰ IFN is the first defence for host and neighbouring cellsto resist virus infection.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2021R1A2C1004131 and RS-2024-00406152)supported by the Institute of Information&Communications Technology Planning&Evaluation(IITP)-ITRC(Information Technology Research Center)grant funded by the Korea government(MSIT)(IITP-2025-RS-2023-00258971,20%,and RS-2023-00228994).
文摘The COVID-19 pandemic has exposed the limitations of traditional preventative measures and underscored the essential role of face masks in controlling virus transmission.More effective and recyclable facial masks using various materials have been developed.In this work,vertically aligned carbon nanotubes(VACNTs)are employed as effective facial mask filters,particularly aimed at preventing SARS-CoV-2 virus infection in preparation for future COVID-19 pandemics.This study assesses six critical aspects of facial masks:hydrophobicity,industrial viability,breathability,hyperthermal antiviral effect,toxicity,and reusability.The VACNT alone exhibits superhydrophobicity with a contact angle of 175.53◦,and an average of 142.7◦for a large area on spun-bonded polypropylene.VACNTs are processed using a roll-to-roll method,eliminating the need for adhesives.Due to the aligned tubes,VACNT filters demonstrate exceptional breathability and moisture ventilation compared to previously reported CNT and conventional filters.Hyperthermal tests of VACNT filters under sunlight confirm that up to 99.8%of the HCoV 229E virus denatures even in cold environments.The safety of using VACNTs is corroborated through histopathological evaluation and subcutaneous implantation tests,addressing concerns of respiratory and skin inflammation.VACNT masks efficiently transmit moisture and rapidly return to their initial dry state under sunlight maintaining their properties after 10000 bending cycles.In addition,the unique capability of VACNT filters to function as respiratory sensors,signaling dampness and facilitating reuse,is assessed,alongside their Joule heating effect.
基金Supported by the National Natural Science Foundation of China (No.30772871)
文摘Objective：To explore the potential effects of berberine on influenza virus infection both in vitro and in vivo.Methods：In vitro anti-influenza virus assays were performed by cytopathogenic effect and neuraminidase assays in Madin Darby canine kidney cells.In vivo anti-influenza virus assays were performed on the viral pneumonia model of mice.The numbers of mice that died within day 2 to day 14 postinfection were recorded to calculate the mortality.On days 2,4,and 6,the viral titers in the lungs were determined by hemagglutination assay;hematoxylin/eosin staining was used to assess the pathogenic changes of lung tissues; the concentrations of tumor necrosis factor-alpha（TNF-α） and monocyte specific chemoattractant molecule （MCP-1） were measured by radio immunoassay or enzyme-linked immunosorbent assay;the concentrations of nitric oxide（NO） and inducible nitric oxide synthetase（iNOS） were detected by colorimetric method;reverse transcription polymerase chain reaction was used to detect the mRNA level of TNF-αand MCP-1.Results： Berberine showed inhibitory effects on cytopathogenic effects and neuraminidase activity of virus,with the therapeutic index 9.69.In vivo,berberine decreased mice mortality from 90%to 55%,reduced virus titers in the lungs on day 2 postinfection（P0.05）.The lung histology scores were 1.50±0.67,4.50±1.00,and 5.50±1.00 in the berberine group on days 2,4,and 6,respectively,which were significantly reduced compared to 2.17±0.22,6.83±0.44,and 8.50±0.33 in the infected group（P0.05）.The productions of NO and iNOS were repressed by berberine compared with those in the infected group（P0.01）.The transcription and expression of TNF-αwere inhibited by berberine on day 4（P0.01） and day 6（P0.05）,and those of MCP-1 were inhibited on day 6（P0.01） compared with the infected group.Conclusions：Berberine exhibited antiviral effects on the influenza virus both in vitro and in vivo.The possible therapeutic mechanism of berberine on influenza-induced viral pneumonia might be inhibiting the virus infection,as well as improving the pathogenic changes by repressing inflammatory substances release
文摘Engineering complex nanocomposites that specifically target the hepatitis B virus （HBV） and overcome the limitations of current therapies such as limited efficacy and serious side effects is very challenging. Here, for the first time, the antiviral effect of engineered plasmonic gold and layered double hydroxide self-assemblies （AuNPs/LDHs） is demonstrated, using HBV as a model virus and hepatoma-derived HepG2.2.215 ceils for viral replication, assembly, and secretion of infectious virions and subviral particles. AuNPs/LDHs were obtained by a simple, cost-effective procedure in which small AuNPs （-3.5 nm） were directly obtained and organized on the surface of larger LDH nanoparticles （-150 nm） by exploiting the capability of MgLDH, ZnLDH, and MgFeLDH to manifest their ＂structural memory＂ in the aqueous solution of Au（O2CCH3）3. The self-assembly approach of AuNPs and LDHs was assessed by transmission electron microscopy （TEM）, X-ray photoelectron spectroscopy （XPS）, powder X-ray diffraction （PXRD）, and UV-Vis analysis （UV-Vis）. All AuNPs/LDHs tested reduced the amount of viral and subviral particles released from treated cells by up to 80% and exhibited good cytocompatibility. AuNPs/MgFeLDH showed the highest antiviral HBV response with more than 90% inhibition of HBV secretion for the whole concentration range. Preliminary studies on the mechanism of HBV inhibition reveals that in the presence of AuNPs/LDHs, HBV particles are sequestered within the treated cells. The antiviral and low cytotoxic plasmonic properties of these Au/LDH nanocomposites indicate that they hold significant potential to be tailored as novel efficient therapeutics for the treatment of hepatitis B.
文摘Oligodeoxynucleotides (Oligomers) including modified and unmodified, homo-and heterooligomers were tested for their ability to inhibit mouse SRS leukemia virus (SRSV)-induced proliferation of cells, colony formation, syncytium formation and reverse transcriptase (RT) activity in vitro. Phosphorothioate analogs complementary to Mo-MuLV sequences, as well as noncomplementary homooligomers, were found to be active. Unmodified homooligomer (dC14) also showed inhibition of growth of ascitic lymphoma carrying SRS virus. Our study suggests that different classes of oligonucleotides may inhibit SRSV replication with different mechanisms.
文摘Turmeric is an herbal plant that is widely used as a traditional herbal medicine in many countries. Curcumin displays its anti-viral activities through several mechanisms of action. In this case report we present a 10-year-old child with herpetic vesiculo-ulcerative lesions who was treated with turmeric along with systemic acyclovir which resulted in complete healing by the third day of application.
文摘Severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)is a novel coronavirus identified at the end of 2019.It is recognized as the causative agent of coronavirus disease 2019(COVID-19).Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19.The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2.The Web of Science,PubMed,Scopus,and Google Scholar were searched using keywords:“COVID-19”,“SARS-CoV-2”,“Kaempferol”and“Quercetin”in the Title/Abstract.Relevant published articles in the English language until August 2020 were considered.Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel(3a channel)expressed in SARS-CoV infected cells.They also reduced the level of reactive oxygen species,expression of inducible nitric oxide synthase,pro-inflammatory mediators including TNF-α,IL-1α,IL-1β,IL-6,IL-10,and IL-12 p70,and chemokines.Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral,antioxidant,anti-inflammatory,and immunomodulatory effects.
文摘Propolis is a natural substance made from resins collected from trees and plants, and which bees combine with pollen, wax, and their own enzymes. It has a complex chemical composition that varies with the harvest season, vegetation type, bee species, and geographical region. Thanks to its components, it has valuable biological properties such as antifungal, antibacterial, anticancer, antiviral, and immunomodulatory activity. For this study, a sample of propolis harvested in April 2019 was used, which came from a bee native to Mexico (<span style="white-space:nowrap;"><i>Plebeia frontalis</i></span>) in whose geographical environment there are seven other native species. Canine distemper virus is an RNA virus that causes a systemic infection with high fatality rates in vips without protective immunity. In this work, the antiviral effect of <span style="white-space:nowrap;"><i>Plebeia frontalis</i></span> propolis on canine distemper virus was tested, administering it one hour before and simultaneously to infection. The antiviral effect was evaluated by determining cellular viability with the MTT assay. The results obtained show that this propolis has a statistically significant antiviral effect on both treatments, although it is slightly better when applied one hour before viral infection, so we can recommend it as an antiviral treatment in both domestic animals and human beings. There are currently few studies of the antiviral effect of propolis, this being the first study of a melliponium propolis in veterinary medicine.
基金supported by Key Program of the Joint Fund of the National Natural Science Foundation of China(No.U20A20135)。
文摘Objective:To screen the anti-SFTSV drugs from 1430 FDA-approved drugs via mini-genome system,and to investigate which stage of the infection process could be suppressed by the identified drugs.Methods:The SFTSV mini-genome system was used to screen drugs with inhibitory effect on SFTSV replication and transcription,and the 50%inhibitory concentration(IC_(50))of each drug was calculated by drug concentration gradient inhibition experiment.Drugs were used to pre-incubate with virus and then incubate with cells,to incubate with virus and cells simultaneously,to incubate with cells after virus invading into cells,or to incubate during the whole infection process,and then qRT-PCR was used to measure the viral RNA copies in the culture supernatant.These experiments were performed to quantitatively determine the inhibition effects of drugs on SFTSV indifferent stages of the whole process including virion stability,entry and post-entry stages,so as to clarify the inhibition mechanism of these drugs.Results:Four drugs including Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide,and Vidofludimus were identified having efficient inhibitory effects on SFTSV RNA replication via minigenome system,with the IC_(50) of 0.014μmol/L,0.627μmol/L,1.283μmol/L,and 0.059μmol/L,respectively.All four drugs showed effective inhibition when adding during the whole SFTSV infection process as well as the post-entry stage.Conclusion:Mycophenolate mofetil,Mycophenolic acid,Nitazoxanide and Vidofludimus show efficient anti-viral effects on SFTSV infection.
基金Key Science and Technology Project of Hainan Province(No.ZDKJ202003)Hainan Provincial Natural Science Foundation of China(No.821QN262)+1 种基金Hainan Provincial Natural Science Foundation of China(No.2019RC207)Hainan Provincial Natural Science Foundation of China(No.820RC628)。
文摘Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.
基金Hainan Provincial Natural Science Foundation of China(No.818MS070)。
文摘Objective:To study the antiviral activity of Guanhuang Ganmao Keli on human respiratory syncytial virus(RSV)in vitro. Methods:The Guanhuang Ganmao Keli was dissolved in pure water and filtered by a 0.22 micron filter to get solution. Cyclopiazonic acid(CPA)was used as positive control. The toxicity of Guanhuang Ganmao Keli on Hep-2 cells was tested by cell counting kit 8(CCK-8). The protective effect of Guanhuang Ganmao Keli on RSV was evaluated under the highest toxic concentration. Results:The TC50 and EC50 of Guanhuang Ganmao Keli is 0.647 mg/mL and 0.014 mg/mL,respectively. Guanhuang Ganmao Keli showed significant antiviral effect when added 0、2、4、6 and 8 h post-infection. Conclusion:Guanhuang Ganmao Keli is an effective antiviral agent on RSV in vitro.
基金the Modern Agricultural Industrial Technology System of the Ministry of Agriculture and Rural Affairs and the Ministry of FinanceProject of Fundamental Research Funds for Jilin Provincial Public Welfare Research Institutes(JSCYJK202102).
文摘[Objectives]To study the toxic effect and antiviral activity of anthraquinone extract of Polygonum cuspidatum on infection of Koi herpes virus(KHV).[Methods]The MTT method and CPE microscopy were used to detect the common carp brain(CCB)cytotoxicity of the P.cuspidatum anthraquinone extract in 48 h.Eight groups of different concentrations of the P.cuspidatum anthraquinone extract 1.96,3.91,7.28,15.63,31.25,62.5,125,250μg/mL experimental groups and a control group without drug effect were set up.After determining the maximum non-toxic range of the P.cuspidatum anthraquinone extract,the viral replication inhibition test was carried out.[Results]The concentration of the P.cuspidatum anthraquinone extract 31.25μg/mL was recognized as the maximum non-toxic concentration.The survival rate of CCB cells was higher than 80%,and the toxic dose(CC50)of the drug for 50%cell death was(72.67±2.12)μg/mL.The maximum inhibition rate of the P.cuspidatum anthraquinone extract was 78.63%±5.47%at a concentration of 31.25μg/mL,and the 50%effective drug dose(IC50)for inhibiting the virus was(13.67±0.47)μg/mL,and the therapeutic index(TI)was 5.48±0.49.In the direct virus killing test,the highest virus inhibition rate was 32.21%.[Conclusions]Under the experimental conditions,it can be concluded that the P.cuspidatum anthraquinone extract has high anti-KHV activity,and at the same time.It is expected to lay a theoretical foundation for the research of P.cuspidatum anthraquinone extract against KHV.
基金financially supported by the Key R&D Special Project of Henan Province,China (241111110300)the National Natural Science Foundation of China (32402849)+2 种基金the Department of Henan Science and Technology,China (252102110035)the Doctoral Research Initiation Fund of Henan University of Animal Husbandry and Economy,China (2022HNUAHEDF033)Key Research Projects of Higher Education Institutions in Henan Province,China (25A150025)。
文摘Innate immunity is the primary defense against viral infections,with Toll-like receptors(TLRs) playing a crucial role in this process.This study aims to highlight the effectiveness of a pyrrolo[3,2-d]pyrimidine derivative(named TLR713),a potential TLR7 agonist,in inhibiting pseudorabies virus(PRV) replication both in vitro and in vivo.Tests on PK-15 cells demonstrated that TLR713 had no significant impact on cell viability,cell cycle progression,or apoptosis at concentrations of 0–3 μmol L^(–1).TLR713 could promote the phosphorylation of IκBα,p38,and JNK through TLR7,and increase the expression of inflammatory cytokines.In vitro,when cells were treated with TLR713,PRV proliferation was inhibited via TLR7 pathway.Analysis of the viral life cycle indicated that TLR713 could inhibit the replication of PRV,but not affect viral attachment,entry,assembly,or release.In vivo,TLR713 showed no side effects on mice at a concentration of 25 mg kg^(–1).It improved the survival rate of PRV-infected mice,reduced tissue viral load,and alleviated the inflammatory response.In summary,this study highlights the potential of TLR713 as a novel TLR7 agonist capable of inhibiting PRV replication and may offer new opportunities for developing antiviral therapies.
基金supported by the National Key Research and Development Program(Grant No.2021YFD1800101)the National Natural Science Foundation of China(Grant No.32072830)+5 种基金Gansu Provincial Major project for science and technology development(Grant No.20ZD7NA006)State Key Laboratory of Veterinary Etiological Biology,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences(Grant No.SKLVEB2020CGPY02)Natural Science Foundation of Gansu Province(Grant No.21JR1RA21421JR7RA018)Basic scientific research business expenses budget incremental project,Chinese Academy of Agricultural Sciences,Lanzhou Veterinary Research Institute(Grant Nos 1610312021002)National Agricultural Science and Technology Innovation Program(CAAS-ASTIP-2016-LVRI).
文摘African swine fever virus(ASFV)is an important pathogen that causes a highly contagious and lethal disease in swine,for which neither a vaccine nor treatment is available.The DNA repair enzyme 8-oxoguanine DNA glycosylase 1(OGG1),which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine(8-oxoG),has been linked to the pathogenesis of different diseases associated with viral infections.However,the role of OGG1-base excision repair(BER)in ASFV infection has been poorly investigated.Our study aimed to characterize the alteration of host reactive oxygen species(ROS)and OGG1 and to analyse the role of OGG1 in ASFV infection.We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1.Viral yield,transcription level,and protein synthesis were reduced in ASFV-infected primary alveolar macrophages(PAMs)treated by TH5487 or SU0268 inhibiting OGG1.The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs.Furthermore,OGG1 was found to negatively regulate interferonβ(IFN-β)production during ASFV infection and IFN-βcould be activated by OGG1 inhibition with TH5487 and SU0268,which blocked OGG1 binding to 8-oxoG.Additionally,the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-βproduction to further affect ASFV replication.These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection.
文摘Coronavirus disease 2019(COVID-19)infection is unequivocally the worst crisis in recent decades,which is caused by a severe acute respiratory virus 2.Currently,there is no effective therapy for the COVID-19 infection.Different countries have different guidelines for treating COVID-19 in the absence of an approved therapy for COVID-19.Therefore,there is an imminent need to identify effective treatments,and several clinical trials have been conducted worldwide.Both hydroxychloroquine[HCQS],chloroquine,and azithromycin(AZ)have been widely used for management based on in vitro studies favoring antiviral effects against the COVID-19 virus.However,there is evidence both in favor and against the use of hydroxychloroquine and azithromycin(HCQS+AZ)combination therapy to manage the COVID-19 infection.The combination of hydroxychloroquine and azithromycin was significantly associated with increased adverse events.However,the inference of these findings was from observational studies.Therefore,large randomized trials are imperative to show the future path for the use of HCQS+AZ combination therapy.However,owing to the ban on HCQS use in COVID-19,this may no longer be essential.This review is on the pharmacology,trials,regimens,and side effects of hydroxychloroquine and azithromycin combination therapy.
基金JG is supported by the Robert W.Storr Bequest to the Sydney Medical Foundation,The University of Sydney,National Health and Medical Research Council of Australia(NHMRC)Program Grants(APP1053206,APP1149976)Investigator and MRFF grants(GNT2032407,NCRI000183,GNT2016215,GNT2010795,GNT1196492)a Cancer Institute,NSW grant(2021/ATRG2028)
文摘The world is witnessing seismic shifts in the landscape of liver disease aetiologies encountered in clinical practice.In part,this is due to effective antiviral therapeutics complimented by sound public health policy,the combination of which has been highly successful in controlling hepatitis B and in reducing the burden of chronic hepatitis C.Unfortunately,economic prosperity,rising living standards and changes in dietary patterns and physical activity have heralded a new era of liver diseases defined by rising rates of metabolic syndrome and consequent metabolic dysfunction associated fatty liver disease(MAFLD).
