Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the ac...Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.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
Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their struct...Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.展开更多
Dear Editor,The 2015–2016 outbreak of Zika virus(ZIKV)fever,first reported in Brazil during early 2015(Zanluca et al.,2015),has infected millions of people and is a global public health concern.ZIKV infections are as...Dear Editor,The 2015–2016 outbreak of Zika virus(ZIKV)fever,first reported in Brazil during early 2015(Zanluca et al.,2015),has infected millions of people and is a global public health concern.ZIKV infections are associated with fetal microcephaly,as well as neurological展开更多
A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhi...A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity.Notably,compound 8f showed the highest SI value(17.1)to Cox B3 virus.Compound 14f showed both potent inhibitory activity against influenza A(IC_(50)=7.53μmol/L)and the highest SI value(12.1).SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities.Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses.展开更多
Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as ...Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as fever,inflammation,and pharyngalgia both in adults and children.However,the instruction manual does not specify the exact usage and dosage of AOL for children.In this article,we set 6 dosage ranges:0.2,0.5,0.7,0.9,1.1,1.4 mL/kg/d,according to its dosage for adults and the conversion method between adult and children dosage.And six animal models were used to evaluate the effectiveness of AOL in different doses.The results indicated that AOL could reduce the lung index,virus load,and expression of proinflammatory cytokines in the lung.AOL could improve pathological changes and prolong the survival time of mice infected by the Influenza A virus(H1N1)A/PR/8/34 strains at 0.5–0.9 mL/kg/d concentrations in different degrees.The four dose groups of 0.7–1.4 mL/kg/d could significantly inhibit the ear shell swelling caused by xylene and reduce the rabbit body temperature induced by lipopolysaccharide(P<0.01,P<0.05).All the five dosage groups of 0.2–1.1 mL/kg/d could inhibit the increase of peritoneal capillary permeability induced by glacial acetic acid(P<0.01).AOL at 0.7 and 0.9 mL/kg/d reduced the painful writhing times in young mice induced by glacial acetic(P<0.01).These results indicated that the optimal dose of AOL in antiviral,antipyretic,anti-inflammatory,and analgesic effects is 0.7 mL/kg/d.展开更多
BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,...BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.展开更多
Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 4...Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.展开更多
The perennial herbaceous plant Euphorbia jolkinii(Euphorbiaceae)is a noxious weed widely distributed in the grasslands of northwestern Yunnan and has greatly threatened the local biodiversity.Phytochemical investigati...The perennial herbaceous plant Euphorbia jolkinii(Euphorbiaceae)is a noxious weed widely distributed in the grasslands of northwestern Yunnan and has greatly threatened the local biodiversity.Phytochemical investigation on the fresh roots of E.jolkinii afforded six new diterpenoids 1,2,4–6,and 8,together with fifteen known diterpenoids.Their structures were elucidated on the basis of 1D and 2D NMR and other spectroscopic methods.Casbane,lathyrane,abietane,and ent-kaurane diterpenoids were reported from this plant for the first time.Selected compounds were evaluated for their antifeedant and anti-RSV(respiratory syncytial virus)activities.Compound 2 and ingenol(3)exhibited moderate antifeedant activity against a generalist insect herbivore,Spodoptera exigua,with EC50 values of 17.88 and 17.71 lg/cm2 respectively.Compound 19 showed significant anti-RSV activity,with 50%inhibition(IC50)value of 10.0 lM and selective index of 8.0.Compounds 1 and 2 were less active against RSV virus,both with IC50 value of 25 lM,and with selective indices of 1.0 and 3.2 respectively.These findings provided new evidence for the biological functions and utilization of the diversified diterpenoid metabolites in the roots of this rich but harmful plant.展开更多
Genital herpes, usually caused by Herpes Simplex Virus type-2 (HSV-2), is the commonest sexually transmitted disease especially amongst rural women in Southern Africa including Zimbabwe. This predisposes them to HIV/A...Genital herpes, usually caused by Herpes Simplex Virus type-2 (HSV-2), is the commonest sexually transmitted disease especially amongst rural women in Southern Africa including Zimbabwe. This predisposes them to HIV/AIDS infection, cancer and opportunistic infections (OIs). Current antiviral treatments are often cytotoxic and/or ineffective. This motivates active research to find alternative safer drugs or lead drugs from traditional medicinal sources. Twenty six (26) methanol extracts from commonly used and often endangered plant species (14) used by communities and traditional medical practitioners for treating illnesses and sexually transmitted diseases from 5-selected districts of Zimbabwe were investigated for toxicity by Brine shrimp lethality test (BSLT) and by 50% Cytopathic effect on VERO cultured cells. The extracts were also tested for antiviral activity against Herpes Simplex Virus-2 (HSV-2) by the End Point Titration Technique (EPTT) and Neutralisation Test (NT) on VERO cells. Results from the BSLTs ranged 66.66 - 4304 μg/ml;50% Cytopathic effect from 19.53 - 312 μg/ml whilst the NT ID<sub>50</sub> values ranged from 10.41 - 125 μg/ml. The antiviral EPTT reduction factor (RF) was 1 - 10<sup>4</sup> with 13 extracts showing RF ≥ 10<sup>3</sup>. All the plant extracts had moderate to high toxicity (LC<sub>50</sub>, 789 - 66 μg/ml) in the BSLT. Six extracts had LC<sub>50</sub> values greater than 1000 μg/ml. All 26 extracts were cytotoxic with CC<sub>50</sub> values < 500 ug/ml of which 19 were more toxic CC<sub>50</sub> in vitro therapeutic indexes ≥ 3.7. Cassia abbreviata, Dichrostachys cinerea and Hypoxis hemerocallidea had therapeutic indexes (TI) 7.5 - 15.0. The more active plant extracts were from roots and root tubers. The results confirm the rationale for the use of traditional medicinal plants by traditional medical practitioners for treating various diseases and could bring awareness for their better use and improve conservation. The results also provide an opportunity to develop more efficacious drugs by isolating lead compounds and determining their mode of action.展开更多
In the modern science, priority is given for the search of biological active compounds with specific properties. As a result of experimental data, it was found that in the reaction between N-(<em>β</em>-D...In the modern science, priority is given for the search of biological active compounds with specific properties. As a result of experimental data, it was found that in the reaction between N-(<em>β</em>-D-glycopyranosyl)-semicarbazide and the Lawesson reagent (2,4-bis(p-methoxyphenyl)-1,3-dithiadiphosphetane 2,4-disulfide) at the ratio 1:1 in pyridine when boiling under reflux in a water bath for 20 - 35 minutes, a new synthetic compound N-(<em>β</em>-D-glycopyranosyl)-thiosemicarbazide is formed. The individuality and structure of the target products were confirmed by 13C NMR spectroscopy, 1H NMR spectroscopy, IR spectroscopy, and elemental analysis. For the synthesized new compounds of N-(<em>β</em>-D-glycopyranosyl)-thiosemicarbazides, the probability of pharmacological and toxic effects were predicted by the computer method in silico. From the synthesized compounds N-(<em>β</em>-D-galactopyranosyl)-thiosemicarbazide, the probability of antibacterial (antibacterial) activity is predicted (<em>Pa</em>/<em>Pi</em> 0.544/0.013). The antibacterial activity of the compound (4) was confirmed in a test for salmonella infection of lambs, salmonellosis of calves, and colipathogenic E. coli serotypes. An experimental study by the in vitro method made it possible to conclude that the new synthetic compound N-(<em>β</em>-D-galactopyranosyl)-thiosemicarbazide in the studied concentrations has a pronounced bactericidal and bacteriostatic effect. The synthetic new compound N-(<em>β</em>-D-glyco- pyranosyl)-thiosemicarbazide is a promising compound for further study.展开更多
Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection...Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection,and treatment is very well tolerated with a duration of 8-12 wk.This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages,identifying some clinically relevant hot topics.First,do the rates of virological response remain as high when patients with more advanced cirrhosis are considered?Large studies have shown slightly lower but still satisfactory rates of response in these patients.Nevertheless,modified schedules with an extended treatment duration and use of ribavirin may be necessary.Second,does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer?Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis.In contrast,the risk of recurrence seems to be unaffected by viral clearance;however,DAA treatment improves survival because of the reduced risk of progression of liver disease.Third,can HCV treatment also have favorable effects on major comorbidities?HCV eradication is associated with a reduced incidence of diabetes,an improvement in glycemic control and a decreased risk of cardiovascular events;nevertheless,a risk of hypoglycemia during DAA treatment has been reported.Finally,is it safe to treat patients with HCV/hepatitis B virus(HBV)coinfection?In this setting,HCV is usually the main driver of viral activity,while HBV replication is suppressed.Because various studies have described HBV reactivation after HCV clearance,a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.展开更多
OBJECTIVE Human metapneumovirus(hMPV)is semblable to respiratory syncytial virus(RSV)which causes respiratory infections typically characterized by cough,runny nose,fever,and nasal congestion but sometimes progressing...OBJECTIVE Human metapneumovirus(hMPV)is semblable to respiratory syncytial virus(RSV)which causes respiratory infections typically characterized by cough,runny nose,fever,and nasal congestion but sometimes progressing to bronchiolitis and pneumonia.Whereas,there is no corresponding drug to inhabit the virus.Studies of new compounds with potential anti-HMPV activity could produce clinical value.Chinese herbal medicine played a great role during COVID-19,therefore we choose some small molecular(JH001)extracted from botany to investigate therapeutic effect on hMPV and the underlying mechanisms.METHODS In this study,16HBE cells were used as a model to explore in vitro antiviral effect.Cytotoxicity assays were performed before the antiviral tests,cell viability of 16HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8(CCK-8).Then RT-qPCR,immunofluorescence,and flow cytometer were used to test the viral titer after cells infected with hMPV.Eventually,6-8 weeks mice were infected intranasally with 60μL of hMPV,the control group was treated with 0.9%saline water,other groups were administered with JH001 and ribavirin,then the lung virus titer and protective effect in lung were judged.RESULTS The obtained JH001 exhibited no cytotoxicity to 16HBE cells during 6.25-200μmol·L^(-1).RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline.And fluorescence exhibited distinct decrease of hMPV-N protein,flow cytometer results showed that MFI decrease evidently.Significant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group,which indicated that JH001 probably had protective and therapeutic effect on viral replication.CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against hMPV and JH001 might be worthy of further development and used as a potential therapeutic strategy for other respiratory viruses in the future.展开更多
Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(...Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(%)were calculated by Celltiter-GLO Assay for evaluating CC50,EC50 and SI values.To observe the drug resistance of the virus to different concentrations of Hehuan Yin within 72 hours by detecting luciferase activity,western-blot was used to detect the protein expression levels of NS5A,NS3 and NS5B.Results:the CC50,EC50 and SI of Hehuan Yin against HCV2a were 132.50g/ml,1.90g/ml and 67.90 respectively.The EC50 after 24h,48h and 72h administration were 18g/ml,5.8g/ml and 2.3g/ml respectively.Within the range of drug concentration,the aqueous extract Hehuan Yin had inhibitory effect on the expression of NS5A and NS5B proteins in a dose-effect relationship,but had no obvious effect on the expression of NS3 protein.Conclusion:The aqueous extract of Hehuan Yin may inhibit the replication of HCV2a virus by changing the protein expression levels of NS5A and NS5B,and the virus has no tolerance to the aqueous extract of Hehuan Yin.展开更多
The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine an...The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine and reviews its action mechanism and toxicological action. It is concluded that the medicinal prospect of matrine is very broad, but more basic research and clinical trials are needed for more comprehensive evaluation.展开更多
The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative m...The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative measures,pharmaceutical intervention is also crucial.Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS‐CoV‐2 and other coronaviruses.In this study,we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels,as well as molecular separation and characterization,to screen and identify natural products with antiviral activity.Using this workflow,we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods.We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS‐CoV‐2 infection and receptor binding domain‐human angiotensin‐converting enzyme 2(RBD‐hACE2)binding in vitro.Following charge‐and size‐based characterization of the active compounds through filtration and chromatographic fractionation,mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition.Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID‐19 and other diseases.展开更多
New viral infections,due to their rapid spread,lack of effective antiviral drugs and vaccines,kill millions of people every year.The global pandemic SARS-CoV-2 in 2019-2021 has shown that new strains of viruses can wi...New viral infections,due to their rapid spread,lack of effective antiviral drugs and vaccines,kill millions of people every year.The global pandemic SARS-CoV-2 in 2019-2021 has shown that new strains of viruses can widespread very quickly,causing disease and death,with significant socio-economic consequences.Therefore,the search for new methods of combating different pathogenic viruses is an urgent task,and strategies based on nanoparticles are of significant interest.This work demonstrates the antiviral adsorption(virucidal)efficacy of nanoparticles of porous silicon(PSi NPs)against various enveloped and non-enveloped pathogenic human viruses,such as Influenza A virus,Poliovirus,Human immunodeficiency virus,West Nile virus,and Hepatitis virus.PSi NPs sized 60 nm with the average pore diameter of 2 nm and specific surface area of 200 m^(2)/g were obtained by ball-milling of electrochemically-etched microporous silicon films.After interaction with PSi NPs,a strong suppression of the infectious activity of the virus-contaminated fluid was observed,which was manifested in a decrease in the infectious titer of all studied types of viruses by approximately 104 times,and corresponded to an inactivation of 99.99%viruses in vitro.This sorption capacity of PSi NPs is possible due to their microporous structure and huge specific surface area,which ensures efficient capture of virions,as confirmed by ELISA analysis,dynamic light scattering measurements and transmission electron microscopy images.The results obtained indicate the great potential of using PSi NPs as universal viral sorbents and disinfectants for the detection and treatment of viral diseases.展开更多
Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of e...Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of essential medicines),may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk.It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase(severe acute respiratory syndrome coronavirus 2),like the main mechanism of action of remdesivir.This involves inhibition of late viral protein synthesis,the virion assembly,and the viral polymerase itself.This antiviral effect is dependent on the administration route,with local application resulting in higher drug concentrations at the site of viral replication.This would suggest also trying lung administration of rifampicin by nebulization to increase the drug’s concentration at infection sites while minimizing systemic side effects.Recent in silico studies with a computer-aided approach,found rifampicin among the most promising existing drugs that could be repurposed for the treatment of COVID-19.展开更多
Aurantiadioic acids A(1)and B(2),two new furan-containing polyketides,and aurantoic acid A(3),a new natural product,were isolated from the liquid fermentation of the sika deer dung-derived actinomycete Actinocorallia ...Aurantiadioic acids A(1)and B(2),two new furan-containing polyketides,and aurantoic acid A(3),a new natural product,were isolated from the liquid fermentation of the sika deer dung-derived actinomycete Actinocorallia aurantiaca.The structures of the new compounds were established by extensive spectroscopic methods,including 1D&2D NMR,HRESIMS spectroscopic analysis.The absolute configuration of 3 was assigned by comparison of the specific optical rotations with the reported derivatives.Biological activity evaluations suggested that compounds 1-3 showed weak inhibition on NO production in the murine monocytic RAW 264.7 macrophages with IC_(50)values of 35.8,41.8,45.2μM,respectively.Compound 3 showed weak inhibition on influenza A virus(A/PuertoRico/8/1934,H1N1)with an EC_(50)value of 35.9μM,and a selective index higher than 13.3.展开更多
Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urge...Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urgently needed.The present study shows that kaempferol is a candidate drug for controlling PRV infection,as it possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro.Kaempferol at a concentration of 52.40μmol L^(-1) could decrease PRV-induced cell death by 90%.With an 50%inhibitory concentration(IC50)value of 25.57μmol L^(-1),kaempferol was more effective than acyclovir(positive control)which has an IC50 value of 54.97μmol L^(-1).A mode of action study indicated that kaempferol inhibited viral penetration and replication stages,decreasing viral loads by 4-and 30-fold,respectively.Addition of kaempferol within 16 h post infection(hpi)could significantly inhibit virus replication,and viral genome copies were decreased by almost 15-fold when kaempferol was added at 2 hpi.Kaempferol regulated the NF-κB and MAPKs signaling pathways involved in PRV infection and changed the levels of the target genes of the MAPKs(ATF-2 and c-Jun)and NF-κB(IL-1α,IL-1βand IL-2)signaling pathways.The findings of the current study suggest that kaempferol could be an alternative measure to control PRV infection.展开更多
基金supported by Project of Zhejiang Basic Public Benefit Research of Zhejiang Province (NO.LGF22Y145002)。
文摘Objective:To evaluate the antiviral activity of pure compounds against herpes simplex virus type 1(HSV-1)from the rhizome of Anemarrhena asphodeloides.Methods:Bioassay-guided isolation was conducted to separate the active compound and its chemical structure was elucidated by spectral analysis.In vitro antiviral efficacy of active compound was detected by Cell Counting Kit-8 assay,plaque reduction assay,and fluorescence observation.RT-PCR was used to determine the viral load and the cytokine-related gene expression after HSV-1 infection.In vivo study was also conducted to further determine antiviral efficacy of an active compound against HSV-1.Results:An active compound was isolated and elucidated as mangiferin.Mangiferin significantly inhibited the replication of HSV-1 in Vero cells with a half maximal inhibitory concentration(IC_(50))of 64.0 mg/L.Time-of-addition and time-of-removal assays demonstrated that mangiferin could effectively inhibit the replication of HSV-1 in the early stage(8 h).UL12,UL42,and UL54 gene expression levels of HSV-1 in the 64 mg/L mangiferin-treated group were markedly reduced as compared with the HSV-1 group(P<0.01).Fluorescence observation showed that mangiferin attenuated the mitochondrial damage maintainingΔΨm induced by HSV-1 in Vero cells.The expression of inflammatory factors TNF-α,IL-1β,and IL-6 was remarkably increased in the virus-infected group as compared with that in the normal group(P<0.05),the levels of these inflammatory factors dropped after treatment with mangiferin.Mangiferin significantly decreased the viral load and attenuated the HSV-1-induced up-regulation of TNF-α,IL-1β,and IL-6.The relative protection rate of HSV-1-infected mice could reach up to55.5%when the concentration of mangiferin was 4 g/kg.Conclusions:Mangiferin exhibits promising antiviral activity against HSV-1 in vitro and in vivo and could be a potential antiviral agent for HSV-1.
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Financial support from the National Natural Sciences Foundation of China(NNSFCgrant Nos.81373287,81630094 and 30825044)is acknowledged
文摘Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.
文摘Dear Editor,The 2015–2016 outbreak of Zika virus(ZIKV)fever,first reported in Brazil during early 2015(Zanluca et al.,2015),has infected millions of people and is a global public health concern.ZIKV infections are associated with fetal microcephaly,as well as neurological
基金This work was supported by the National Natural Science Foundation of China(No.81273439)the National Mega-project for Innovative Drugs(No.2012ZX09301002-001-024-02).
文摘A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities.The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity.Notably,compound 8f showed the highest SI value(17.1)to Cox B3 virus.Compound 14f showed both potent inhibitory activity against influenza A(IC_(50)=7.53μmol/L)and the highest SI value(12.1).SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities.Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses.
基金support of ABSL-2 biosafety laboratory of the Institute of Chinese Materia Medica.National Natural Science Foundation of China(No.82104500)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021B015).
文摘Antiviral Oral Liquid(AOL)is an adult medicine in the Chinese Pharmacopoeia used to treat upper respiratory infections such as influenza.It has shown promising clinical efficacy in relieving flu-like symptoms such as fever,inflammation,and pharyngalgia both in adults and children.However,the instruction manual does not specify the exact usage and dosage of AOL for children.In this article,we set 6 dosage ranges:0.2,0.5,0.7,0.9,1.1,1.4 mL/kg/d,according to its dosage for adults and the conversion method between adult and children dosage.And six animal models were used to evaluate the effectiveness of AOL in different doses.The results indicated that AOL could reduce the lung index,virus load,and expression of proinflammatory cytokines in the lung.AOL could improve pathological changes and prolong the survival time of mice infected by the Influenza A virus(H1N1)A/PR/8/34 strains at 0.5–0.9 mL/kg/d concentrations in different degrees.The four dose groups of 0.7–1.4 mL/kg/d could significantly inhibit the ear shell swelling caused by xylene and reduce the rabbit body temperature induced by lipopolysaccharide(P<0.01,P<0.05).All the five dosage groups of 0.2–1.1 mL/kg/d could inhibit the increase of peritoneal capillary permeability induced by glacial acetic acid(P<0.01).AOL at 0.7 and 0.9 mL/kg/d reduced the painful writhing times in young mice induced by glacial acetic(P<0.01).These results indicated that the optimal dose of AOL in antiviral,antipyretic,anti-inflammatory,and analgesic effects is 0.7 mL/kg/d.
基金Supported by National Natural Science Foundation of China,No.81930110The National Funded Postdoctoral Researcher Program of China,No.GZC20232406+2 种基金Henan Province Traditional Chinese Medicine Science Research Project,No.2023ZY3040Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20230233National Key Research and Development Program of China,No.2022YFC2303103.
文摘BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.
基金supported by the National Natural Science Foundation of China(Grant Number 32260370)Youth Talent Project of Major Academic and Technical Leaders Training Program of Jiangxi Province(Grant Number 20204BCJL23045)+2 种基金Special Research Project on Camphor Tree(KRPCT)of Jiangxi Forestry Department(Grant Number 2020CXZX07)Innovative Leading Talent Short-Term Project in Natural Science Area of Jiangxi Province(Grant Number jxsq2018102072)the Key Research and Development Program of Jiangxi Province(Grant Number 20192BBFL60014).
文摘Turpentine is a renewable and resourceful forest product.The deep processing and utilization of turpentine,particularly its primary componentβ-pinene,has garnered widespread attention.This study aimed to synthesize 40 derivatives ofβ-pinene,including nopinone,3-cyanopyridines of nopinone,myrtanyl acid,myrtanyl acylthioureas,and myrtanyl amides.We assessed the antiviral activities of theseβ-pinene derivatives against influenza virus A/Puerto Rico/8/34(H1N1)using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Theβ-pinene derivatives were used before and after cellular infection with the influenza virus to evaluate their preventive and therapeutic effects against the H1N1 virus.The results showed that only compound 10o exhibited a preventive effect against the H1N1 virus with a half-maximal inhibitory concentration(IC50)value of 47.6μmol/L.Among the compounds,4e,4i,and 4l demonstrated therapeutic effects against cellular infection,with compound 4e displaying the most potent therapeutic effect(IC50=17.5μmol/L),comparable to the positive control ribavirin.These findings indicated that certainβ-pinene derivatives exhibited in vitro antiviral activity against the H1N1 influenza A virus,warranting further investigation as potential anti-influenza agents.
基金the National Natural Science Foundation of China(31200263)the Youth Innovation Promotion association of Chinese Academy of Sciences(awarded to Shi-Hong Luo)+1 种基金the“Western Light”Program of Chinese Academy of Sciences(awarded to Shi-Hong Luo)the“Hundred Talents Program”of Chinese Academy of Sciences(awarded to Sheng-Hong Li).
文摘The perennial herbaceous plant Euphorbia jolkinii(Euphorbiaceae)is a noxious weed widely distributed in the grasslands of northwestern Yunnan and has greatly threatened the local biodiversity.Phytochemical investigation on the fresh roots of E.jolkinii afforded six new diterpenoids 1,2,4–6,and 8,together with fifteen known diterpenoids.Their structures were elucidated on the basis of 1D and 2D NMR and other spectroscopic methods.Casbane,lathyrane,abietane,and ent-kaurane diterpenoids were reported from this plant for the first time.Selected compounds were evaluated for their antifeedant and anti-RSV(respiratory syncytial virus)activities.Compound 2 and ingenol(3)exhibited moderate antifeedant activity against a generalist insect herbivore,Spodoptera exigua,with EC50 values of 17.88 and 17.71 lg/cm2 respectively.Compound 19 showed significant anti-RSV activity,with 50%inhibition(IC50)value of 10.0 lM and selective index of 8.0.Compounds 1 and 2 were less active against RSV virus,both with IC50 value of 25 lM,and with selective indices of 1.0 and 3.2 respectively.These findings provided new evidence for the biological functions and utilization of the diversified diterpenoid metabolites in the roots of this rich but harmful plant.
文摘Genital herpes, usually caused by Herpes Simplex Virus type-2 (HSV-2), is the commonest sexually transmitted disease especially amongst rural women in Southern Africa including Zimbabwe. This predisposes them to HIV/AIDS infection, cancer and opportunistic infections (OIs). Current antiviral treatments are often cytotoxic and/or ineffective. This motivates active research to find alternative safer drugs or lead drugs from traditional medicinal sources. Twenty six (26) methanol extracts from commonly used and often endangered plant species (14) used by communities and traditional medical practitioners for treating illnesses and sexually transmitted diseases from 5-selected districts of Zimbabwe were investigated for toxicity by Brine shrimp lethality test (BSLT) and by 50% Cytopathic effect on VERO cultured cells. The extracts were also tested for antiviral activity against Herpes Simplex Virus-2 (HSV-2) by the End Point Titration Technique (EPTT) and Neutralisation Test (NT) on VERO cells. Results from the BSLTs ranged 66.66 - 4304 μg/ml;50% Cytopathic effect from 19.53 - 312 μg/ml whilst the NT ID<sub>50</sub> values ranged from 10.41 - 125 μg/ml. The antiviral EPTT reduction factor (RF) was 1 - 10<sup>4</sup> with 13 extracts showing RF ≥ 10<sup>3</sup>. All the plant extracts had moderate to high toxicity (LC<sub>50</sub>, 789 - 66 μg/ml) in the BSLT. Six extracts had LC<sub>50</sub> values greater than 1000 μg/ml. All 26 extracts were cytotoxic with CC<sub>50</sub> values < 500 ug/ml of which 19 were more toxic CC<sub>50</sub> in vitro therapeutic indexes ≥ 3.7. Cassia abbreviata, Dichrostachys cinerea and Hypoxis hemerocallidea had therapeutic indexes (TI) 7.5 - 15.0. The more active plant extracts were from roots and root tubers. The results confirm the rationale for the use of traditional medicinal plants by traditional medical practitioners for treating various diseases and could bring awareness for their better use and improve conservation. The results also provide an opportunity to develop more efficacious drugs by isolating lead compounds and determining their mode of action.
文摘In the modern science, priority is given for the search of biological active compounds with specific properties. As a result of experimental data, it was found that in the reaction between N-(<em>β</em>-D-glycopyranosyl)-semicarbazide and the Lawesson reagent (2,4-bis(p-methoxyphenyl)-1,3-dithiadiphosphetane 2,4-disulfide) at the ratio 1:1 in pyridine when boiling under reflux in a water bath for 20 - 35 minutes, a new synthetic compound N-(<em>β</em>-D-glycopyranosyl)-thiosemicarbazide is formed. The individuality and structure of the target products were confirmed by 13C NMR spectroscopy, 1H NMR spectroscopy, IR spectroscopy, and elemental analysis. For the synthesized new compounds of N-(<em>β</em>-D-glycopyranosyl)-thiosemicarbazides, the probability of pharmacological and toxic effects were predicted by the computer method in silico. From the synthesized compounds N-(<em>β</em>-D-galactopyranosyl)-thiosemicarbazide, the probability of antibacterial (antibacterial) activity is predicted (<em>Pa</em>/<em>Pi</em> 0.544/0.013). The antibacterial activity of the compound (4) was confirmed in a test for salmonella infection of lambs, salmonellosis of calves, and colipathogenic E. coli serotypes. An experimental study by the in vitro method made it possible to conclude that the new synthetic compound N-(<em>β</em>-D-galactopyranosyl)-thiosemicarbazide in the studied concentrations has a pronounced bactericidal and bacteriostatic effect. The synthetic new compound N-(<em>β</em>-D-glyco- pyranosyl)-thiosemicarbazide is a promising compound for further study.
文摘Since molecules with direct-acting antiviral(DAA)became available,the landscape of the treatment of hepatitis C virus(HCV)infection has completely changed.The new drugs are extremely effective in eradicating infection,and treatment is very well tolerated with a duration of 8-12 wk.This review aims to report the outstanding clinical benefits of DAA and to highlight their critical disadvantages,identifying some clinically relevant hot topics.First,do the rates of virological response remain as high when patients with more advanced cirrhosis are considered?Large studies have shown slightly lower but still satisfactory rates of response in these patients.Nevertheless,modified schedules with an extended treatment duration and use of ribavirin may be necessary.Second,does the treatment of HCV infection affect the risk of occurrence and recurrence of liver cancer?Incidence is reduced after viral eradication but remains high enough to warrant periodic surveillance for an early diagnosis.In contrast,the risk of recurrence seems to be unaffected by viral clearance;however,DAA treatment improves survival because of the reduced risk of progression of liver disease.Third,can HCV treatment also have favorable effects on major comorbidities?HCV eradication is associated with a reduced incidence of diabetes,an improvement in glycemic control and a decreased risk of cardiovascular events;nevertheless,a risk of hypoglycemia during DAA treatment has been reported.Finally,is it safe to treat patients with HCV/hepatitis B virus(HBV)coinfection?In this setting,HCV is usually the main driver of viral activity,while HBV replication is suppressed.Because various studies have described HBV reactivation after HCV clearance,a baseline evaluation for HBV coinfection and a specific follow-up is mandatory.
文摘OBJECTIVE Human metapneumovirus(hMPV)is semblable to respiratory syncytial virus(RSV)which causes respiratory infections typically characterized by cough,runny nose,fever,and nasal congestion but sometimes progressing to bronchiolitis and pneumonia.Whereas,there is no corresponding drug to inhabit the virus.Studies of new compounds with potential anti-HMPV activity could produce clinical value.Chinese herbal medicine played a great role during COVID-19,therefore we choose some small molecular(JH001)extracted from botany to investigate therapeutic effect on hMPV and the underlying mechanisms.METHODS In this study,16HBE cells were used as a model to explore in vitro antiviral effect.Cytotoxicity assays were performed before the antiviral tests,cell viability of 16HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8(CCK-8).Then RT-qPCR,immunofluorescence,and flow cytometer were used to test the viral titer after cells infected with hMPV.Eventually,6-8 weeks mice were infected intranasally with 60μL of hMPV,the control group was treated with 0.9%saline water,other groups were administered with JH001 and ribavirin,then the lung virus titer and protective effect in lung were judged.RESULTS The obtained JH001 exhibited no cytotoxicity to 16HBE cells during 6.25-200μmol·L^(-1).RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline.And fluorescence exhibited distinct decrease of hMPV-N protein,flow cytometer results showed that MFI decrease evidently.Significant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group,which indicated that JH001 probably had protective and therapeutic effect on viral replication.CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against hMPV and JH001 might be worthy of further development and used as a potential therapeutic strategy for other respiratory viruses in the future.
基金Natural Foundation of Guangdong Province(No.2018A030313308)。
文摘Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(%)were calculated by Celltiter-GLO Assay for evaluating CC50,EC50 and SI values.To observe the drug resistance of the virus to different concentrations of Hehuan Yin within 72 hours by detecting luciferase activity,western-blot was used to detect the protein expression levels of NS5A,NS3 and NS5B.Results:the CC50,EC50 and SI of Hehuan Yin against HCV2a were 132.50g/ml,1.90g/ml and 67.90 respectively.The EC50 after 24h,48h and 72h administration were 18g/ml,5.8g/ml and 2.3g/ml respectively.Within the range of drug concentration,the aqueous extract Hehuan Yin had inhibitory effect on the expression of NS5A and NS5B proteins in a dose-effect relationship,but had no obvious effect on the expression of NS3 protein.Conclusion:The aqueous extract of Hehuan Yin may inhibit the replication of HCV2a virus by changing the protein expression levels of NS5A and NS5B,and the virus has no tolerance to the aqueous extract of Hehuan Yin.
文摘The natural alkaloids extracted from Chinese herbal medicine have shown high medicinal value in vivo and in vitro, such as bacteriostasis, anti-virus, anti-tumor and anti-inflammation. This paper focuses on matrine and reviews its action mechanism and toxicological action. It is concluded that the medicinal prospect of matrine is very broad, but more basic research and clinical trials are needed for more comprehensive evaluation.
基金supported by grants from the Beijing Academy of Agriculture and ForestrSy cience (KJCX20230411 and KJCX20230211)National Natural Science Foundation of China (NSFC T2225005,22050004,21927802,21974069)+1 种基金Ministry of Science and Technology of the People's Republic of China (2018YFA0800200)Open Fund Programs of Shenzhen1 Bay Laboratory (SZBL2020090501001).
文摘The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative measures,pharmaceutical intervention is also crucial.Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS‐CoV‐2 and other coronaviruses.In this study,we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels,as well as molecular separation and characterization,to screen and identify natural products with antiviral activity.Using this workflow,we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods.We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS‐CoV‐2 infection and receptor binding domain‐human angiotensin‐converting enzyme 2(RBD‐hACE2)binding in vitro.Following charge‐and size‐based characterization of the active compounds through filtration and chromatographic fractionation,mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition.Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID‐19 and other diseases.
基金The research was funded by the Russian Science Foundation(Grant number 20-12-00297).
文摘New viral infections,due to their rapid spread,lack of effective antiviral drugs and vaccines,kill millions of people every year.The global pandemic SARS-CoV-2 in 2019-2021 has shown that new strains of viruses can widespread very quickly,causing disease and death,with significant socio-economic consequences.Therefore,the search for new methods of combating different pathogenic viruses is an urgent task,and strategies based on nanoparticles are of significant interest.This work demonstrates the antiviral adsorption(virucidal)efficacy of nanoparticles of porous silicon(PSi NPs)against various enveloped and non-enveloped pathogenic human viruses,such as Influenza A virus,Poliovirus,Human immunodeficiency virus,West Nile virus,and Hepatitis virus.PSi NPs sized 60 nm with the average pore diameter of 2 nm and specific surface area of 200 m^(2)/g were obtained by ball-milling of electrochemically-etched microporous silicon films.After interaction with PSi NPs,a strong suppression of the infectious activity of the virus-contaminated fluid was observed,which was manifested in a decrease in the infectious titer of all studied types of viruses by approximately 104 times,and corresponded to an inactivation of 99.99%viruses in vitro.This sorption capacity of PSi NPs is possible due to their microporous structure and huge specific surface area,which ensures efficient capture of virions,as confirmed by ELISA analysis,dynamic light scattering measurements and transmission electron microscopy images.The results obtained indicate the great potential of using PSi NPs as universal viral sorbents and disinfectants for the detection and treatment of viral diseases.
文摘Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of essential medicines),may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk.It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase(severe acute respiratory syndrome coronavirus 2),like the main mechanism of action of remdesivir.This involves inhibition of late viral protein synthesis,the virion assembly,and the viral polymerase itself.This antiviral effect is dependent on the administration route,with local application resulting in higher drug concentrations at the site of viral replication.This would suggest also trying lung administration of rifampicin by nebulization to increase the drug’s concentration at infection sites while minimizing systemic side effects.Recent in silico studies with a computer-aided approach,found rifampicin among the most promising existing drugs that could be repurposed for the treatment of COVID-19.
基金This work was financially supported by National Natural Science Foundation of China(Grant No.81773590).The authors thank Analytical&Measuring Centre,South-Central University for Nationalities,for the NMR measurements.
文摘Aurantiadioic acids A(1)and B(2),two new furan-containing polyketides,and aurantoic acid A(3),a new natural product,were isolated from the liquid fermentation of the sika deer dung-derived actinomycete Actinocorallia aurantiaca.The structures of the new compounds were established by extensive spectroscopic methods,including 1D&2D NMR,HRESIMS spectroscopic analysis.The absolute configuration of 3 was assigned by comparison of the specific optical rotations with the reported derivatives.Biological activity evaluations suggested that compounds 1-3 showed weak inhibition on NO production in the murine monocytic RAW 264.7 macrophages with IC_(50)values of 35.8,41.8,45.2μM,respectively.Compound 3 showed weak inhibition on influenza A virus(A/PuertoRico/8/1934,H1N1)with an EC_(50)value of 35.9μM,and a selective index higher than 13.3.
基金This work was supported by the Program of Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(SCCXTD-2020-18)the Science and Technology Project of Sichuan Province,China(2018NZ0043,2018NZ0064 and 2018HH0076).
文摘Pseudorabies virus(PRV),in the family Herpesviridae,is a pathogen of Aujeszky’s disease,which causes great economic losses to the pig industry.Recent outbreaks of Pseudorabies imply that new control measures are urgently needed.The present study shows that kaempferol is a candidate drug for controlling PRV infection,as it possesses the ability to inhibit PRV replication in a dose-dependent manner in vitro.Kaempferol at a concentration of 52.40μmol L^(-1) could decrease PRV-induced cell death by 90%.With an 50%inhibitory concentration(IC50)value of 25.57μmol L^(-1),kaempferol was more effective than acyclovir(positive control)which has an IC50 value of 54.97μmol L^(-1).A mode of action study indicated that kaempferol inhibited viral penetration and replication stages,decreasing viral loads by 4-and 30-fold,respectively.Addition of kaempferol within 16 h post infection(hpi)could significantly inhibit virus replication,and viral genome copies were decreased by almost 15-fold when kaempferol was added at 2 hpi.Kaempferol regulated the NF-κB and MAPKs signaling pathways involved in PRV infection and changed the levels of the target genes of the MAPKs(ATF-2 and c-Jun)and NF-κB(IL-1α,IL-1βand IL-2)signaling pathways.The findings of the current study suggest that kaempferol could be an alternative measure to control PRV infection.