Toxicity and Antiviral Activities of Some Medicinal Plants Used by Traditional Medical Practitioners in Zimbabwe

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 ID50 values ranged from 10.41 - 125 μg/ml. The antiviral EPTT reduction factor (RF) was 1 - 104 with 13 extracts showing RF ≥ 103. All the plant extracts had moderate to high toxicity (LC50, 789 - 66 μg/ml) in the BSLT. Six extracts had LC50 values greater than 1000 μg/ml. All 26 extracts were cytotoxic with CC50 values < 500 ug/ml of which 19 were more toxic CC50 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.

Aromatic compounds from an aqueous extract of “ban lan gen” and their antiviral activities

A pair of new diphenyl glycerol ether enantiomers(-)-l and(+)-l and two new methyl benzamidobenzoates 2 and 3,named(-)-(R)-and(+)-(S)-isatindigotrioic acid[(-)-l and(+)-l]and isatindigoticamides A(2) and B(3),respectively,were isolated from an aqueous decoction of the roots of Isatis indigotica(ban lan gen).Their structures were elucidated by spectroscopic data analysis including2 D NMR experiments.The absolute configurations of(-)-l and(+)-l were assigned based on the CD exciton chirality method.Compounds 2 and 3 exhibited antiviral activities against HSV-1 with IC_(50)values of 4.87 and 25.87μmol/L,respectively.Compound 2 was also found active against Coxsackie virus B3 and LPS-induced NO production.

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cucumber mosaic virus（CMV） in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/m L, which was superior to ningnanmycin（409.3 mg/m L）.

Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

A novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71(EV71)and the coxsackievirus B3(CVB3)and B6(CVB6)were evaluated.Compounds 7d and 9b showed potent antiviral activities against EV71 with ICso values of 8.27 and 5.48μM,respectively.Compound 7f,which has been synthesized for the first time in this work,showed the highest level of inhibitory activity against both CVB3 and CVB6 with an ICso value of 0.62 and 0.87μM.Compounds 4b,7a,9c and 9e also showed strong inhibitory activities against both the CVB3 and CV B6 at low concentrations(IC_(50)=1.42-7.15μM),whereas compounds 4d,7c,7e and 7g showed strong activity against CVB6(IC_(50)=2.91-3.77μM)together with low levels of activity against CVB3.Compound 7d exhibited stronger inhibitory activity against CVB3(IC_(50)=6.44μM)thaln CVB6(IC_(50)>8.29μM).The thioflavone derivatives 7a,7c,7d,7e,7f and 7g,represent a new class of lead compounds for the development of novel antiviral agents.

Antiviral activity of mangiferin from the rhizome of Anemarrhena asphodeloides against herpes simplex virus type 1

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.

Pharmacodynamic study in multi-animal models on the efficacy and optimal dosage of antiviral oral liquid for children

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.

Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet

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.

Antifeedant and Antiviral Diterpenoids from the Fresh Roots of Euphorbia jolkinii

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.

Antiviral Activity of Dual-acting Hydrocarbon-stapled Peptides against HIV-1 Predominantly Circulating in China

Objective New rationally designed i,i＋7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China. Methods The antiviral activity of three i,i＋7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRFOI_AE isolates was evaluated in peripheral blood mononuclear cells （PI3MCs）. The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells. Results We found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication （ICso） in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the ICs0s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67. Conclusion Hydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.

Direct antiviral agents in hepatitis C virus related liver disease:Don’t count the chickens before they’re hatched

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.

Study of Guanhuang Ganmao Keli on the antiviral activity on human respiratory syncytial virus

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.

Antiviral Activity of Silkworm Expressed Recombinant Human Macrophage Colony-Stimulating Factor in Vitro and Its Mechanism

Cells, pretreated with the recombinant human macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm larvae, were inoculated with several viruses to observe the effect of rhM-CSF on viral replication. The results showed that in cultures of fibroblast derived from human fetal skin-muslce tissues infected with the viruses (including VSV, rhinovirus, influenza virus type A3, HSV-1, HSV-2, adenovirus type 6 and type 11), rhM-CSF inhibited the virus-induced cytopathy, which defered or relieved the cytophathy and that in the cells derived from breast feeding rabbit kidney infected with HSV-1, rhM-CSF reduced titer of the virus in a rhM-CSF dose-dependent pattern,in which rhM-CSF with the dose of 1×106 U/L made the viral titer drop dwon over 200 times. This antiviral activity of rhM-CSF could be partially neutralized by anti-IFN-βMcAb, but not by antiTNF-α, anti-IFN-α, or anti-IFA-γ McAb, indicating the mechanism of the antiviral activity of MCSF is related to the induction of IFN-β.

Advances in Pharmacology and Toxicology of Marine

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.

Separation and Anti-Hantaan Virus Activity of Extracts from Alternanthera philoxcroides in vitro and in vivo

A water-soluble substance was extracted from the Chinese herb, Alternantheraphiloxcroides with hot water and alcohol. Aliquots of this initial extract were further fractionated by treatment with ether, ethyl acetate and alcohol respectively. The four extracts were assayed for anti-viral activity against three serum, Hantaan virus 114 （HV114）, HV435 and A9 strains. Results show that the four extracts are capable of inhibiting Hantaan virus propagation, of which extract No. 1 has the best efficiency. The three dosage of extract No. 1, which are used upon three Hantaan virus serum IC50, are 153, 157, 154 μg/mL. New-born mice were made to be infected with HV114 and then fed in vivo with extract No.l on the 3rd, 10th and 14th days after being infected by the virus. The treatment continued for 8 days with a dosage of 2.5 g/kg. Result shows that survival rates of mice were 75%, 50% and 0, respectively. The median time to death （MTDs） of the three groups were 37, 30, 23 days.

Synthesis and Biological Activity of New Pyrethroid Acid Oxime-esters Containing Pyrazole Ring

A series of compounds containing oxime-ester linkage and pyrazole ring(in place of the ester linkage and the alcohol moiety in pyrethroid ester) was designed and synthesized. The structures of all the compounds prepared were confirmed by 1H NMR and MS spectroscopy as well as elemental analyses. The bioassay data of those compounds against tobacco mosaic virus(TMV), cucumber mosaic virus(CMV), potato virus X(PVX) and potato virus Y(PVY) were presented. Among them compound 6i was found to possess significant plant antiviral activities. But all the compounds showed low insecticidal and acaricidal activities.

Synthesis, Assessment of Biological Activity and Toxicity for N-(<i>β</i>-D-Glycopyranosyl)-Thiosemicarbazides

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-(β-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-(β-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-(β-D-glycopyranosyl)-thiosemicarbazides, the probability of pharmacological and toxic effects were predicted by the computer method in silico. From the synthesized compounds N-(β-D-galactopyranosyl)-thiosemicarbazide, the probability of antibacterial (antibacterial) activity is predicted (Pa/Pi 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-(β-D-galactopyranosyl)-thiosemicarbazide in the studied concentrations has a pronounced bactericidal and bacteriostatic effect. The synthetic new compound N-(β-D-glyco- pyranosyl)-thiosemicarbazide is a promising compound for further study.

Synthesis,Bioactivity and Crystal Structure Analysis of Diisopropyl[(4-cyanopyrazol-3-ylamino)(2-hydroxyl-phenyl) methyl]phosphonate

The title compound,diisopropyl[（4-cyanopyrazol-3-ylamino）（2-hydroxylphenyl） -methyl] phosphonate was synthesized by the addition reaction of diisopropyl phosphite and N-（4-cyanopyrazole-3-yl） -2-hydroxylphenyl-imine. Its structure was characterized by IR,1H NMR,elemental analysis and single-crystal X-ray diffraction. The crystal belongs to the triclinic system,space group P1^- with a = 9.1840（13） ,b = 9.2278（13）,c = 12.1952（17） A,α = 93.846（2） ,β = 90.947（2） ,γ = 111.289（2） °,V = 959.9（3） A^3,Dc = 1.309 g/cm^3,Z = 2,μ（MoKa） = 0.173,F（000） = 400,the final R = 0.0414 and wR = 0.1196 for 2985 observed reflections（I 〉 2σ（I）） . The pyrazole and benzene moieties are approximately coplanar in each case. The dihedral angle between planes 1 and 2 is 82.99°. The crystal structure is stabilized by three intermolecular hydrogen bonds of O（1） -H（1） …O（2） ,N（2） -H（2） …N（3） and N（2） -H（2） …O（1） . Preliminary bioassay indicated that the title compound possessed antiviral activity to some extent.

Rifampicin for COVID-19

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.

In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs

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.

Three New Compounds from the Actinomycete Actinocorallia aurantiaca

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.