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1.
Article in Chinese | WPRIM | ID: wpr-909577

ABSTRACT

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, immunofluores?cence, and flow cytometer were used to test the viral titer after cells infected with hMPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL 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 - 200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluo?rescence exhibited distinct decrease of hMPV-N protein, flow cytometer results showed that MFI decrease evidently. Sig?nificant 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 fur?ther development and used as a potential therapeutic strategy for other respiratory viruses in the future.

2.
Acta Pharmaceutica Sinica ; (12): 1429-1433, 2021.
Article in Chinese | WPRIM | ID: wpr-887079

ABSTRACT

Two dimeric diterpenoid alkaloids were isolated from the whole plant of Aconitum tanguticum (Maxim.) Stapf and their structures were elucidated by extensive analysis of 1D, 2D-NMR and HR-MS data. One is a new compound and named tanguticurine A (1), and the other is the known compound anthoroidine B (2); both were isolated from this plant for the first time. The antiviral activity of compounds 1 and 2 against HCV and EV71 were also evaluated. It was found that compound 1 had a good inhibitory effect on HCV and EV71 with EC50 values of 15.5 and 9.7 μmol·L-1, respectively, and showed low cytotoxicity. Therefore, compound 1 is a good antiviral lead compound and deserves further study.

3.
Acta Pharmaceutica Sinica ; (12): 793-798, 2021.
Article in Chinese | WPRIM | ID: wpr-876516

ABSTRACT

Dengue virus (DENV) is the most rapidly transmitted mosquito-borne pathogen, which is the main cause of seasonal outbreaks of dengue fever and dengue hemorrhagic fever in tropical and subtropical regions, and may cause serious life-threatening diseases. There is an urgent need to develop effective vaccines or antiviral therapies. In this paper, we found that a podocarpane-type diterpenoid, (3α,5β,10α)-13-methoxypodocarpa-8,11,13-triene-3,12-diol (MPTD), isolated from the stems and leaves of Aleurites moluccana, showed good effect against DENV. The anti-DENV activity of MPTD against four different DENV serotypes was studied by plaque assay. The cytotoxicity of MPTD in Vero and Huh7 cells was tested by MTT assay. qRT-PCR and Western blot assays were used to investigate the anti-DENV activity of MPTD at RNA and protein levels, respectively. The results showed that MPTD greatly reduced the virus titer in DENV infected Vero cells, and its 50% effective concentration (EC50) for DENV (1–4) were 2.72 ± 0.39, 10.99 ± 5.18, 18.72 ± 0.21, and 0.48 ± 0.28 μmol·L-1, respectively. The results showed that MPTD inhibits DENV RNA level and the expression of E protein. In addition, MPTD may inhibit the early stage of DENV replication and exert antiviral activity. Further studies showed that the inhibitory effect of MPTD against DENV infection is not targeting the viral entry stage. Therefore, MPTD has a significant anti-dengue virus effect, and is an anti-DENV compound with potential application value.

4.
J. venom. anim. toxins incl. trop. dis ; 27: e20210039, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1351021

ABSTRACT

Background Hepatitis C virus (HCV) infection is a major worldwide health problem that can cause liver fibrosis and hepatocellular carcinoma (HCC). The clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) that are usually expensive and have side effects. Therefore, achieving the discovery of more successful agents is always urgent. In this context, antiviral compounds that inhibit viral infections and disease progression with important therapeutic activities have been identified in animal venoms including arthropod toxins. This indicates that arthropod venoms represent a good natural source of promising candidates for new antivirals. Methods The antiviral activity of the wasp venom (WV), isolated from the Oriental hornet (Vespa orientalis), was assessed using cell culture technique with human hepatocellular carcinoma-derived cell line (Huh7it-1) and the recombinant strain of HCV genotype 2a (JFH1). Results The results revealed that WV inhibited HCV infectivity with 50% inhibitory concentration (IC50) of 10 ng/mL, while the 50% cytotoxic concentration (CC50) was 11,000 ng/mL. Time of addition experiment showed that the WV blocked HCV attachment/entry to the cells probably through virucidal effect. On the other hand, the venom showed no inhibitory effect on HCV replication. Conclusion WV can inhibit the entry stage of HCV infection at non-cytotoxic concentrations. Therefore, it could be considered a potential candidate for characterization of natural anti-HCV agents targeting the entry step.(AU)


Subject(s)
Antiviral Agents , Wasp Venoms , Carcinoma, Hepatocellular
5.
Rev. colomb. ciencias quim. farm ; 49(1): 218-233, Jan.-Apr. 2020. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1144348

ABSTRACT

SUMMARY Chalcones highlights as an important structure in medicinal chemistry and thus has been widely used as a template in the development of new drugs. In this study, we aim to determine the antibacterial, anti-Candida, and anti-Dengue potential of new chalcone-bearing 2,4-dihydroxyl and tetrahydropyranyl moieties. Antimicrobial activity assays showed that microorganism of the Staphylococcus genus (including methicillin-resistant strains) were susceptible to 2,4-dihydroxychalcones, with minimum inhibitory concentrations (MICs) ranging of 19.5 to 125 µg.mL-1. Compound 4e, which showed the highest bacteriostatic effect, also has bactericidal activity from of 80 µg.mL-1. The growth of oral isolates of Candida albicans was also efficiently inhibited with compound 4e (MIC: 15.6-32.3 µg.mL-1), which was fungicidal at 15.6 µg.mL-1. However, the presence of the tetrahydropyranyl moiety impaired both the antibacterial and antifungal effects. None of the chalcones tested were actives against Dengue virus serotype 2. In conclusion, the compound 4e showed good anti-Staphylococci and anti-Candida activity and may be a promising prototype for the development of new antimicrobial agents.


RESUMEN Las chalconas se destacan como una estructura importante en la química médica y, por lo tanto, se ha empleado como prototipo para el desarrollo de nuevos fármacos. En este estudio, nuestro objetivo fue determinar el potencial antibacteriano, anti Candida y anti-Dengue de las nuevas chalconas que poseen los grupos 2,4-dihidroxilo y tetrahidropiranilo. El ensayo de actividad antimicrobiana mostró que las bacterias del género Staphylococcus (incluidas las cepas resistentes a la meticilina) fueron sensibles a las 2,4-dihidroxicalconas estudiadas, con concentraciones inhibitorias mínimas (CIM) que oscilan entre 19,5 y 125 µg.mL-1. El compuesto 4e, que tuvo el mejor efecto bacteriostático, también mostró un efecto bactericida a partir de la concentración de 80 µg.mL-1. El crecimiento de los aislamientos orales de Candida albicans también se inhibió eficientemente con el compuesto 4e (CIM: 15.6-32.3 µg.mL-1), que fue fungicida a una concentración de 15.6 µg.mL-1. Sin embargo, la presencia del grupo tetrahidropiranilo perjudicó la actividad antibacteriana y anti-fúngica de los análogos de la chalcona. Además, ninguno de los compuestos evaluados mostró un efecto contra el virus del dengue serotipo 2. En conclusión, el compuesto 4e muestra una buena actividad anti-estafilocócica y anti-Candida y puede ser un prototipo prometedor para el desarrollo de nuevos agentes antimicrobianos.


RESUMO As chalconas se destacam como uma importante estrutura na química medicinal e dessa forma tem sido empregada como um protótipo para o desenvolvimento de novos fármacos. Nesse estudo, nós objetivamos determinar o potencial antibacteriano, anti-Candida, e anti-Dengue de novas chalconas que possuem os grupos 2,4-dihidroxil e tetrahidropiranil. O ensaio de atividade antimicrobiana mostrou que bactérias do gênero Staphylococcus (incluindo linhagens resistentes a meticilina) foram sensíveis para as 2,4-dihidroxichalconas estudadas, com concentrações inibitórias mínimas (CIM) variando de 19,5 para 125 Dengue potential of new chalcone µg.mL-1. O composto 4e, o qual apresentou o melhor efeito bacteriostático, também mostrou efeito bactericida a partir da concentração de 80 µg.mL-1. O crescimento de isolados orais de Candida albicans foi também eficientemente inibido com o composto 4e (CIM: 15.6-32.3 µg.mL-1), o qual foi fungicida a concentração de 15,6 µg.mL-1. Entretanto, a presença do grupo tetrahidropiranil prejudicou a atividade antibacteriana e antifúngica dos análogos de chalcona. Adicionalmente, nenhum dos compostos avaliados mostrou efeito contra o vírus da dengue sorotipo 2. Em conclusão, o composto 4e apresenta boa atividade anti-estafilocóccica e anti-Candida, e pode ser um promissor protótipo para o desenvolvimento de novos agentes antimicrobianos.

6.
Article | IMSEAR | ID: sea-210735

ABSTRACT

Two new geldanamycin derivatives such as 17-(tryptamine)-17-demethoxygeldanamycin (2) andC17 methoxyl of geldanamycin (1). Their antiviral activity was evaluated based on influenza virus propagation inembryonated chicken eggs and viral absorption by hemagglutination (HA) inhibition test. The findings indicatedthat these compounds inhibited viral propagation at a concentration of 12.5 µg/ml. For the viral absorption, onlycompounds 2 and 3 inhibited HA at a concentration of 50 µg/ml. The solubility of compounds 2 and 3 in waterwas 290 and 306 µM, higher than that of compound 1 about 1.91 and 2.01 times, respectively. The compounds 2and 3 showed a moderate cytotoxic activity on LLC-MK2 and Vero cells with IC50 values of >200.00 µg/ml. Theseresults demonstrated the invention of tryptamine-geldanamycin hybrids to prevent influenza virus infection in viralabsorption and viral propagation steps.

7.
Acta Pharmaceutica Sinica B ; (6): 344-357, 2020.
Article in English | WPRIM | ID: wpr-787624

ABSTRACT

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.

8.
Acta Pharmaceutica Sinica B ; (6): 512-528, 2020.
Article in English | WPRIM | ID: wpr-792992

ABSTRACT

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

9.
Article in Chinese | WPRIM | ID: wpr-846715

ABSTRACT

Euphorbiae Ebracteolatae Radix is the dry root of plant Euphorbia fischeriana or E. ebracteolata of Euphorbiaceae, which is a widely utilized natural medicine with broad development prospect. It has been discovered that Euphorbiae Ebracteolatae Radix contains several biologically active constituents, among which diterpenoids are the most important. The diterpenoids of Euphorbiae Ebracteolatae Radix contain eight types including abietane-type, tigliane-type, pimarane-type, rosane-type, cembrane-type, ent-kaurane-type, ingenane-type and atisane-type. Diterpenoids of Euphorbiae Ebracteolatae Radix have significant anti-tumor, anti-inflammatory, anti-viral and other pharmacological activities. In this paper, the chemical constituents of diterpenoids and pharmacological activities of Euphorbiae Ebracteolatae Radix in recent years were reviewed in order to provide references for better developing the resources of Euphorbiae Ebracteolatae Radix and its clinical application.

10.
Article in Chinese | WPRIM | ID: wpr-846403

ABSTRACT

Since the coronavirus disease 2019 (COVID-19) outbreak, National Health Commission of the People's Republic of China and local departments have released a number of diagnosis and treatment plans for COVID-19. One of the recommended prescriptions for severe stage treatment is Huanglian Jiedu Decoction, whose TCM syndrome is corresponding to the severe syndrome of dual blaze of qi and nutrient in the COVID-19 protocol of Diagnosis and Treatment of Novel Coronavirus Pneumonia (trial version 7). Huanglian Jiedu Decoction can be used in the treatment of syndrome of dual blaze of qi and nutrient. Syndrome of dual blaze of qi and nutrient is with consumption of nutrient yin of body fluid, pathogenic qi always triumphing over healthy qi, excessive noxious heat from qi and nutrient, Huanglian Jiedu Decoction has the efficacy of clearing heat and detoxicating. It can achieve the therapeutic purpose of nourishing yin and protecting yin by removing evil spirits. Modern pharmacological studies have shown that Huanglian Jiedu Decoction has potential effects of anti-inflammatory and antipyretic, antiviral, antioxidant, regulating immunity and protecting viscera and tissues in the treatment of COVID-19 with severe syndrome of dual blaze of qi and nutrient. In this paper, the pathogenesis evolution of COVID-19 with severe syndrome of dual blaze of qi and nutrient, the relationship between prescriptions and syndromes of Huanglian Jiedu Decoction and its modern pharmacological effects was analyzed, so as to provide a basis for the effective treatment of Huanglian Jiedu Decoction in COVID-19 with severe syndrome of dual blaze of qi and nutrient.

11.
Chinese Pharmacological Bulletin ; (12): 508-513, 2020.
Article in Chinese | WPRIM | ID: wpr-856994

ABSTRACT

Aim To investigate the antiviral activity and mechanism of myricetin against enterovirus 71 (E V 7 1) infection. Methods The cytopathic effect (CPE) and plaque assay were used to observe the antiviral effect of myricetin against EV71 in Vero cell. The cells were treated with myricetin at different concentrations combined with crystal violet staining to detectthe cytotoxicity of myricetin. The effect of myricetin on VP1 protein expression was detected by Western blot. The effect of myricetin on VP1 gene expressionwas evaluated byRT-PCR. Results Myricetin pretreatment at 2. 5-20 fimol L-1' significantly inhibitedcell death induced by EV71 infection in a dose-dependent manner with the IC50 value of 5. 6 jxmol • L-1. Compared to virus control group, myricetin could significantly reduce the viral titer at the concentration of 2. 5 ~ 20 u,mol • L-1. The results of Western blot and RT-PCR showed that myricetin could markedlyreduce the gene and protein expression levels of viral capsid protein VP1. Conclusion Myricetin has significant antiEV71 activity in vitro.

12.
China Pharmacy ; (12): 1166-1171, 2020.
Article in Chinese | WPRIM | ID: wpr-821601

ABSTRACT

OBJECTIVE:To eva luate content constituent characteristics and antiviral activity of main flavonnoids in genuine and non-genuine Scutellaria baicalensis ,and to investigate quality-efficiency relationship and effective substance. METHODS : Totally 8 batches of S. baicalensis from different origins (S1-S8)were collected to prepare its water extract lyophilized powder. UPLC method was used to determine the contents of baicalin ,wogonoside,baicalein and wogonin ,and calculate their content constituent ratio. According to the content constituent ratio of flavonoids in S. baicalensis from different origins ,the mixture of the above four components was prepared as the corresponding simulated sample of flavonoids (E1-E8). Using ribavirin as positive control,MTT assay and CPE method were used to investigate half toxic concentration (TD50)of the water extract from 8 batches of S. baicalensis and their corresponding simulated samples to human laryngeal carcinoma cell Hep-2 and their half inhibition concentration(IC50)to respiratory syncytial virus (RSV);treatment indexes (TI)were calculated. Pearson correlation analysis for the content of baicalin ,wogonoside,baicalein and wogonin with their anti-RSV activity (IC50)was performed by SPSS 17.0 software. RESULTS :The contents of baicalin and wogonoside in sample S 4(from Hebei Chengde )were the highest ,and the contents of baicalein and wogonin in sample S 6(from Inner Mongolia- 2)were the highest. The contents of above 4 components were the lowest in sample S 6,S6,S7(from Beijing ),S4. The contents of flavonoid glycosides in sample S 4 were relatively higher, while those of corresponding glycosides were relatively lower ;the content constituent ratio of baicalin , wogonoside,baicalein and wogonin was 1∶0.224∶0.111∶0.013. The contents of flavonoid glycosides in sample S6 wererelatively lower ,while those of glycosides were relatively 126.com higher;the content constituent ratio of above 4 components was 1∶0.241∶0.713∶0.106. TC 50 of S. bai calensis water extracts from different origins to Hep- 2 cells was all higher than 50 μg/mL, IC50 to RSV was 11.11-51.74 μg/mL;TI was 1.86-5.20. TC 50 of corresponding simulated samples of flavonoids was 23.11-52.23 μg/mL,while IC 50 to RSV was 4.87-14.61 μg/mL;TI was 1.85-4.75. The anti-RSV effects of water extract of S 4 from genuine origins(Hebei Chengde )and its corresponding simulated sample E 4 were the strongest. Correlation analysis showed that the correlation coefficient between the contents of 4 flavonoids and antiviral activity was less than 0.5,and there was no significant correlation between them. CONCLUSIONS :When the content constituent ratio of 4 main flavonoids in S. baicalensis was 1∶0.224∶ 0.111 ∶ 0.013,it has a strong inhibition effect on RSV. S. baicalensis from genuine origins has better constituent characteristics of flavonoids,which may be the important material basis for the best antiviral effect of genuine medicinal material.

13.
Acta Pharmaceutica Sinica ; (12): 703-719, 2020.
Article in Chinese | WPRIM | ID: wpr-820866

ABSTRACT

Long-term use of approved antiviral drugs can lead to drug resistance and side effects. On the other hand, there are currently no antiviral drugs or vaccines available to treat some newly emerging virus infections. Therefore, antiviral drugs research has always been a hot research topic in the field of medicinal chemistry. Natural products are an important source of antiviral drugs. This article reviews the progress of antiviral natural products discovered in the past decade to provide potential lead compounds for drug development.

14.
Acta Pharmaceutica Sinica ; (12): 1582-1587, 2019.
Article in Chinese | WPRIM | ID: wpr-780250

ABSTRACT

Tenofovir disoproxil fumarate (TDF) is a nucleoside analogue that has been widely used for clinical treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. The aim of this study was to investigate whether TDF has anti-Zika virus (ZIKV) activity in vitro. The inhibitory effect of TDF on ZIKV was detected by plaque reduction assay. Then, the anti-ZIKV activity of TDF at RNA level and protein level was verified by real time quantitative PCR and Western blot. Finally, MTT assay was used to determine the cytotoxicity of TDF. Our results showed that TDF not only reduced the formation of plaque after ZIKV infection, but also inhibited the replication of ZIKV RNA or expression of ZIKV NS2B protein. The 50% effective concentration (EC50) of TDF in inhibition of ZIKV replication were 14.96-27.47 μmol·L-1, while that of ribavirin was 56.01 ± 12.16 μmol·L-1, which served as the positive control. The cytotoxicity of TDF and ribavirin in Vero cells were very low, with their 50% cytotoxic concentration (CC50) values being greater than 500 μmol·L-1. The therapeutic index of TDF calculated by CC50/EC50 was greater than 18.20, which was significantly higher than that of ribavirin. The results suggest that TDF has good anti-ZIKV activity in vitro and is expected to become a candidate drug for anti-ZIKV therapy.

15.
Article | IMSEAR | ID: sea-194733

ABSTRACT

Viral diseases are the major causes of devastations in the human history and animal farming worldwide. Bacterial and parasitic diseases have been controlled by use of effective disinfectants, antibiotics and antiparasitic agents. Since, viruses are intracellular and any intervention will affect the cellular metabolism of the host, development of antiviral drugs is a challenge. Drugs acting on microbial agents have been mentioned in Ayurvedic texts as Krimighna Dravyas. Tulsi, Ocimum sanctum is one of the most important medicinal plants mentioned in Ayurvedic literature for its medicinal and spiritual properties. The plant is an highly celebrated medicinal plant as “The incomparable one,†“Mother medicine of nature†and “The queen of herbsâ€. Tulsi, along with other health benefits is known to have anti-infective functions. Hence, antiviral activity of aqueous, ethanol, methanol and chloroform extract of powdered drugs was evaluated against economically important viruses of veterinary importance, Orthmyxovirus and Paramyxovirus. The in vitro cytotoxicity confirmed the safety of the extracts and aqueous extract showed no inhibition on paramyxovirus while showing moderate inhibitory activity on orthomyxovirus while ethanol extract showed moderate inhibitory activity on paramyxovirus and no activity on orthomyxoviruses. Methanol extract showed no inhibition of paramyxovirus while showed significant inhibition of orthomyxovirus. Chloroform extract of the plant showed no inhibition paramyxovirus while significant inhibition was observed on orthomyxoviurs. Results of the study suggest that the O. sanctum can be used as antiviral agent for effective control of viral infections of animal importance.

16.
European J Med Plants ; 2018 Feb; 22(2): 1-7
Article | IMSEAR | ID: sea-189377

ABSTRACT

Extract of Nauclea latifolia (NL) root bark collected from the Nigerian flora was examined for anti-RSV activity. Preliminary data showed anti-RSV activities with IC50 =75.62 µg/ml when tested against the recombinant strain rgRSV expressing the green fluorescent protein. Corresponding assays for the cytotoxic effect of the extract against utilized cell lines gave TC50 = 333.82 µg/ml. Further screening of against the circulating RSV A2 strain established their promising anti-RSV utility. Time of additional studies for the elucidation of the possible mechanism of action gave 74.38, 69.42, and 71.90% reduction of RSV plaque forming units at the respective 0, 2, and 4 hours post-infection addition times.

17.
Article in English | WPRIM | ID: wpr-717995

ABSTRACT

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.


Subject(s)
Animals , Asthma , Bronchoalveolar Lavage , Common Cold , Granulocytes , Heat-Shock Proteins , HeLa Cells , Hot Temperature , Humans , In Vitro Techniques , Lung , Mice , Molecular Chaperones , Monocytes , Respiratory System , Rhinovirus , RNA Viruses
18.
Acta Pharmaceutica Sinica B ; (6): 933-943, 2018.
Article in English | WPRIM | ID: wpr-775013

ABSTRACT

Five new sulfur-enriched alkaloids isatithioetherins A-E (-), and two pairs of scalemic enantiomers (+)- and (-)-isatithiopyrin B ( and ) and isoepigoitrin and isogoitrin and ), along with the known scalemic enantiomers epigoitrin and goitrin ( and ), were isolated and characterized from an aqueous extract of the roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory (TDDFT). Compounds - represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Isolation and structure characterization of and support the postulated biosynthetic pathways for the diastereomers and a rare thio-Diels-Alder reaction. Compounds and showed antiviral activity against the influenza virus A/Hanfang/359/95 (H3N2, IC 0.60 and 1.92 μmol/L) and the herpes simplex virus 1 (HSV-1, IC 3.70 and 2.87 μmol/L), and also inhibited Coxsackie virus B3 (IC 0.71 μmol/L).

19.
Acta Pharmaceutica Sinica ; (12): 944-949, 2018.
Article in Chinese | WPRIM | ID: wpr-779955

ABSTRACT

In this study, azvudine (FNC), hydrochloride salt of azvudine (FNC-HCl) and triphosphate azovudine (FNC-TP) were tested against DENV-Ⅱ recombinant virus (DENV-Ⅱ Luc+). The inhibitory activity of FNC, FNC-HCl and FNC-TP on DENVs were detected by plaque assay. The effect on the expression of DENV-Ⅱ envelope protein E was detected by Western blot; the inhibitory of DENV-Ⅱ viral RNA by compounds was detected by real-time quantitative PCR. MTT assay was used to determine the cytotoxicity of the three compounds on Vero cells. The results showed that FNC, FNC-HCl and FNC-TP inhibited the viral replication by inhibition of renilla luciferase activity of DENV-Ⅱ Luc+. The 50% effective concentration (EC50) of FNC, FNC-HCl and FNC-TP in the inhibition of DENVs replication were from 0.54-25.42 μmol·L-1, while that of ribavirin was 40.78 ±1.02 μmol·L-1 as the positive control. Western blot and real time quantitative PCR results showed that FNC, FNC-HCl and FNC-TP significantly inhibited the expression of DENV-Ⅱ E protein, and the replication of DENV-Ⅱ viral RNA. The 50% cytotoxic concentrations of FNC, FNC-HCl and FNC-TP were all greater than 3 000.00 μmol·L-1. The results suggest that in vitro anti-DENVs activities of FNC, FNC-HCl and FNC-TP are superior to ribavirin, which are expected to become new candidates of anti-DENV drugs.

20.
Article in Chinese | WPRIM | ID: wpr-709030

ABSTRACT

Objective To investigate the effect of Andrographis paniculata Nees(APN)extract on Coxsackievirus A16(CVA16)in vitro.Methods African green monkey kidney-derived Vero cells(Vero cells)were treated with APN extract at the concentration of 500.0,250.0,125.0,60.0,30.0,15.0,7.5 and 3.8 μg/mL,the cytotoxicity was determined with cell counting Kit-8 and the IC50was calculated by Probit unit regression method.Direct inactivating activity on CVA16,blocking of CVA16 adsorbing Vero cells and inhibition of CVA16 replication in Vero cells were determined and compared between Ribavirin(RBV) and APN extract with CVA16-infected Vero cells.SPSS 24.0 software was used to analyze the data.Results The selected concentrations of APN extract and RBV for experiment were 15.0, 7.5 and 3.8 μg/mL according to cytotoxicity test.Both of APN extract and RBV had neither direct inactivation on CVA 16 nor blocking of CVA16 adsorbing at the concentration of 15.0,7.5 and 3.8 μg/mL(F=1.54,1.52 and 0.67, 1.68,all P>0.05).However,both drugs had the capability of inhibiting CVA 16 replication in Vero cells at the concentration of 15.0 and 7.5 μg/mL(t=6.87,11.76 and 7.71,12.84,all P<0.05).Conclusion Experimental result shows that APN extract can effectively inhibit CVA 16 replication in Vero cells in vitro.

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