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1.
Simões LR Maciel GM Brandão GC Kroon EG Castilho RO Oliveira AB 《Letters in applied microbiology》2011,53(6):602-607
Aims: To investigate the in vitro antiviral activity of Distictella elongata (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their main components. Methods and Results: The antiviral activity was evaluated against human herpesvirus type 1 (HSV‐1), murine encephalomyocarditis virus (EMCV), vaccinia virus Western Reserve (VACV‐WR) and dengue virus 2 (DENV‐2) by the 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assay. LEE presented anti‐HSV‐1 [EC50 142·8 ± 5·3 μg ml?1; selectivity index (SI) 2·0] and anti‐DENV‐2 activity (EC50 9·8 ± 1·3 μg ml?1; SI 1·5). The pectolinarin ( 1 ) isolated from LEE was less active against HSV‐1 and DENV‐2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids was also obtained. Ursolic and oleanolic acids have shown antiviral activity against HSV‐1. A mixture of pectolinarin ( 1 ) and acacetin‐7‐O‐rutinoside ( 2 ) was isolated from FEE and has presented anti‐DENV‐2 activity (EC50 11·1 ± 1·6 μg ml?1; SI > 45). Besides the antiviral activity, D. elongata has disclosed antioxidant effect. Conclusions: These data shows that D. elongata has antiviral activity mainly against HSV‐1 and DENV‐2, besides antioxidant activity. These effects might be principally attributed to flavonoids isolated. Significance and Impact of the Study: Distictella elongata might be considered a promising source of anti‐dengue fever phytochemicals. 相似文献
2.
3.
Identification of a novel compound targeting the nuclear export of influenza A virus nucleoprotein
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Feng Huang Jingliang Chen Junsong Zhang Likai Tan Gui Lu Yongjie Luo Ting Pan Juanran Liang Qianwen Li Baohong Luo Hui Zhang Gen Lu 《Journal of cellular and molecular medicine》2018,22(3):1826-1839
Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug‐resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti‐influenza compound, ZBMD‐1, from a library of 20,000 compounds using cell‐based influenza A infection assays. We found that ZBMD‐1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC50 ranging from 0.41–1.14 μM. Furthermore, ZBMD‐1 inhibited the polymerase activity and specifically impaired the nuclear export of NP. Further investigation indicated that ZBMD‐1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket. ZBMD‐1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro‐inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that ZBMD‐1 is a promising anti‐influenza compound which can be further investigated as a useful strategy against IAVs in the future. 相似文献
4.
Xiu-ying Pu Jian-ping Liang Xue-hong Wang Tao Xu Lan-ying Hua Ruo-feng Shang Yu Liu Yan-mei Xing 《中国病毒学》2009,24(1):19-27
To study the antiviral effect of Hypericum perforatum L. extract (HPE) on influenza A virus (IAV) (H1N1) in vitro and in vivo. Cytopathic effect (CPE) and neutral red (NR) dye uptake were used to examine the antiviral effect of HPE on Madin Darby
Canine Kidney (MDCK) cells which were infected with IAV in vitro. HPE was effective against influenza A virus (IAV) in vitro, with a 50% effective concentration (EC50) of 40 μg/mL. The mean 50% cytotoxic concentration (CC50) in the MDCK used in these experiments was 1.5 mg/mL. Ribavirin was run in parallel with EC50 values of 5.0 μg/mL; the mean CC50 for ribavirin was 520 μg/mL. Oral gavage administrations of HPE or ribavirin to mice infected with the IAV were highly effective
in preventing death, slowing the decline of arterial oxygen saturation, inhibiting lung consolidation and reducing lung virus
titers. The minimum effective dose of HPE in these studies was 31.25 mg/kg/day, which was administered twice daily for 5 d
beginning 4 h prior to virus exposure. Below a dosage of 2000 mg/kg/day, almost all treated mice survived, which suggests
that HPE is of low toxicity. Ribavirin’s minimum effective dose was 40 mg/kg/day with the LD50 determined to be 200 mg/kg/day.
Delay of the initiation of either HPE or ribavirin therapy, using approximately 1/3 LD50 dose each time, could still be protective as late as 48 h after exposure to the IAV. While both agents appeared to have similar
efficacy against IAV infections, HPE was considered to be less toxic and may warrant further evaluation as a possible therapy
for influenza.
Foundation items: One Hundred Person Project of The Chinese Academy of Sciences (2008-287); The Project of Basic Scientific
Research Fund for Central Public-Welfare of Institute of Sciences (BRF070402). 相似文献
5.
Mina Saeedi Dorrin Mohtadi‐Haghighi Seyedeh Sara Mirfazli Mohammad Mahdavi Roshanak Hariri Hania Lotfian Najmeh Edraki Aida Iraji Omidreza Firuzi Tahmineh Akbarzadeh 《化学与生物多样性》2019,16(2)
In this work, a novel series of arylisoxazole‐phenylpiperazines were designed, synthesized, and evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Our results revealed that [5‐(2‐chlorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5c ) was the most potent AChE inhibitor with IC50 of 21.85 μm . It should be noted that most of synthesized compounds showed no BChE inhibitory activity and [5‐(2‐fluorophenyl)‐1,2‐oxazol‐3‐yl](4‐phenylpiperazin‐1‐yl)methanone ( 5a ) was the most active anti‐BChE derivative (IC50=51.66 μm ). Also, kinetic studies for the AChE and BChE inhibitory activity of compounds 5c and 5a confirmed that they have simultaneously bound to the catalytic site (CS) and peripheral anionic site (PAS) of both AChE and BChE. Furthermore, docking study of compound 5c showed desired interactions of that compound with amino acid residues located in the active and peripheral anionic sites. Compound 5c was also evaluated for its BACE1 inhibitory activity and demonstrated IC50=76.78 μm . Finally, neuroprotectivity of compound 5c on Aβ‐treated neurotoxicity in PC12 cells depicted low activity. 相似文献
6.
Aims: The anti‐enterovirus 71 (EV71) activity of six Nepalese plants’ extracts and gallic acid (GA) isolated from Woodfordia fruticosa Kurz (family; Lythaceae) flowers were evaluated in Vero cells. Methods and Results: The anti‐EV71 activity of tested compounds was evaluated by a cytopathic effect reduction method. Our results demonstrated that flowers’ extracts of W. fruticosa exerted strong anti‐EV71 activity, with a 50% inhibitory concentration (IC50) of 1·2 μg ml?1 and no cytotoxicity at a concentration of 100 μg ml?1, and the derived therapeutic index (TI) was more than 83·33. Rivabirin showed no antiviral activity against EV71. Furthermore, GA isolated from W. fruticosa flowers exhibited a higher anti‐EV71 activity than the extract of W. fruticosa flowers, with an IC50 of 0·76 μg ml?1 and no cytotoxicity at a concentration of 100 μg ml?1, and the derived TI was 99·57. Conclusions: This study demonstrated that flower extracts of W. fruticosa possessed anti‐EV71 activity and GA isolated from these flowers showed stronger anti‐EV71 activity than that the extracts. Significance and Impact of the Study: Our results suggest that the GA from W. fruticosa flowers may be used as a potential antiviral agent. 相似文献
7.
G.C. Brandão E.G. Kroon J.R. Dos Santos J.R. Stehmann J.A. Lombardi A. Braga de Oliveira 《Letters in applied microbiology》2010,51(4):469-476
Aims: To evaluate the antiviral activity of Bignoniaceae species occurring in the state of Minas Gerais, Brazil. Methods and Results: Ethanol extracts of different anatomical parts of bignoniaceous plant species have been evaluated in vitro against human herpesvirus type 1 (HSV‐1), vaccinia virus (VACV) and murine encephalomyocarditis virus (EMCV) by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. A total of 34 extracts from 18 plant species selected according to ethnopharmacological and taxonomic criteria were screened. Fifteen of the 34 extracts (44·1%) have disclosed antiviral activity against one or more of the viruses assayed with EC50 values in the range of 23·2 ± 2·5–422·7 ± 10·9 μg ml?1. Conclusions: Twelve of the 34 extracts (35·3%) might be considered promising sources of antiviral natural products, as they have shown EC50 ≤ 100 μg ml?1. The present screening discloses the high potential of the Bignoniaceae family as source of antiviral agents. Significance and Impact of the Study: Active extracts were identified and deserve bioguided studies for the isolation of antiviral compounds and studies on mechanism of action. 相似文献
8.
Xiu-ying PU Jian-ping LIANG Xue-hong WANG Tao XU Lan-ying HUA Ruo-feng SHANG Yu LIU Yan-mei XING 《中国病毒学》2009,24(1)
To study the antiviral effect of Hypericum perforatum L. extract (HPE) on influenza A virus (IAV) (H1N1) in vitro and in vivo. Cytopathic effect (CPE) and neutral red (NR) dye uptake were used to examine the antiviral effect of HPE on Madin Darby Canine Kidney (MDCK) cells which were infected with IAV in vitro. HPE was effective against influenza A virus (IAV) in vitro, with a 50% effective concentration (EC50) of 40 μg/mL. The mean 50% cytotoxic concentration (CC50) in the MDCK used in these experiments was 1.5 mg/mL. Ribavirin was run in parallel with EC50 values of 5.0 μg/mL; the mean CC50 for ribavirin was 520 μg/mL. Oral gavage administrations of HPE or ribavirin to mice infected with the IAV were highly effective in preventing death, slowing the decline of arterial oxygen saturation, inhibiting lung consolidation and reducing lung virus titers. The minimum effective dose of HPE in these studies was 31.25 mg/kg/day, which was administered twice daily for 5 d beginning 4 h prior to virus exposure. Below a dosage of 2000 mg/kg/day, almost all treated mice survived, which suggests that HPE is of low toxicity. Ribavirin's minimum effective dose was 40 mg/kg/day with the LD50 determined to be 200 mg/kg/day. Delay of the initiation of either HPE or ribavirin therapy, using approximately 1/3 LD50 dose each time, could still be protective as late as 48 h after exposure to the IAV. While both agents appeared to have similar efficacy against IAV infections, HPE was considered to be less toxic and may warrant further evaluation as a possible therapy for influenza. 相似文献
9.
Oleg. I. Artyushin Aleksandra A. Moiseeva Vladimir V. Zarubaev Aleksander V. Slita Anastasiya V. Galochkina Anna A. Muryleva Sophia S. Borisevich Olga I. Yarovaya Nariman F. Salakhutdinov Valery K. Brel 《化学与生物多样性》2019,16(11)
A series of camphecene and quinolizidine alkaloid (?)‐cytisine conjugates has been obtained for the first time using ‘click’ chemistry methodology. The cytotoxicity and virus‐inhibiting activity of compounds were determined against MDCK cells and influenza virus A/Puerto Rico/8/34 (H1N1), correspondingly, in in vitro tests. Based on the results obtained, values of 50 % cytotoxic dose (CC50), 50 % inhibition dose (IC50) and selectivity index (SI) were determined for each compound. It has been shown that the antiviral activity is affected by the length and nature of linkers between cytisine and camphor units. Conjugate 13 ((1R,5S)‐3‐(6‐{4‐[(2‐{(E)‐[(1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐ylidene]amino}ethoxy)methyl]‐1H‐1,2,3‐triazol‐1‐yl}hexyl)‐1,2,3,4,5,6‐hexahydro‐8H‐1,5‐methanopyrido[1,2‐a][1,5]diazocin‐8‐one), which contains cytisine fragment separated from triazole ring by –C6H12– aliphatic linker, showed the highest activity at relatively low toxicity (CC50=168 μmol, IC50=8 μmol, SI=20). Its selectivity index appeared higher than that of reference compound, rimantadine. According to theoretical calculations, the antiviral activity of the lead compound 13 can be explained by its influence on the functioning of neuraminidase. 相似文献
10.
Doan Thanh Hieu Duong Tien Anh Pham‐The Hai Nguyen Thi Thuan Le‐Thi‐Thu Huong Eun Jae Park A. YoungJi Jong SoonKang Phan Thi PhuongDung Sang‐Bae Han Nguyen‐Hai Nam 《化学与生物多样性》2019,16(4)
The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI?H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5b ) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5c ) (IC50 values, 0.10–0.16 μm ) were found to be approximately 30‐fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm ). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide ( 5a ; IC50 values of 0.21–0.38 μm ) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c , strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA. 相似文献
11.
Modification,Biological Evaluation and SAR Studies of Novel 1H‐Pyrazol Derivatives Containing N,N′‐Disubstituted Urea Moiety as Potential Anti‐melanoma Agents
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《化学与生物多样性》2018,15(6)
Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF‐mutant melanoma. In continuation of our earlier studies on anti‐melanoma agents based on 1H‐pyrazole skeleton, two sets of novel compounds that include 1H‐pyrazole‐4‐amines FA 1 – FA13 and corresponding urea derivatives FN 1 – FN13 have been synthesized and evaluated for their BRAFV600E inhibitory and antiproliferation activities. Compound FN 10 displayed the most potent biological activity against BRAFV600E (IC50 = 0.066 μm ) and the A375 human melanoma cell line (GI50 = 0.81 μm ), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H‐pyrazole‐3‐amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole‐based anti‐melanoma agents. 相似文献
12.
Discovery of a New Class of Inhibitors of Vaccinia Virus Based on (−)‐Borneol from Abies sibirica and (+)‐Camphor
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Anastasiya S. Sokolova Olga I. Yarovaya Nikolay I. Bormotov Larisa N. Shishkina Nariman F. Salakhutdinov 《化学与生物多样性》2018,15(9)
A series of the bornyl ester/amide derivatives with N‐containing heterocycles were designed and synthesized as vaccinia virus (VV) inhibitors. Bioassay results showed that among the designed compounds, derivatives 6 , 13 , 14 , 34 , 36 and 37 showed the best inhibitory activity against VV with the IC50 values of 12.9, 17.9, 3.4, 2.5, 12.5 and 7.5 μm , respectively, and good cytotoxicity. The primary structure–activity relationship (SAR) study suggested that the combination of a saturated N‐heterocycle, such as morpholine or 4‐methylpiperidine, and a 1,7,7‐trimethylbicyclo[2.2.1]heptane scaffold was favorable for antiviral activity. 相似文献
13.
Myrna Adianti Chie Aoki Mari Komoto Lin Deng Ikuo Shoji Tutik Sri Wahyuni Maria Inge Lusida Soetjipto Hiroyuki Fuchino Nobuo Kawahara Hak Hotta 《Microbiology and immunology》2014,58(3):180-187
Development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still much needed from clinical and economic points of view. Antiviral substances obtained from medicinal plants are potentially good targets to study. Glycyrrhiza uralensis and G. glabra have been commonly used in both traditional and modern medicine. In this study, extracts of G. uralensis roots and their components were examined for anti‐HCV activity using an HCV cell culture system. It was found that a methanol extract of G. uralensis roots and its chloroform fraction possess anti‐HCV activity with 50%‐inhibitory concentrations (IC50) of 20.0 and 8.0 μg/mL, respectively. Through bioactivity‐guided purification and structural analysis, glycycoumarin, glycyrin, glycyrol and liquiritigenin were isolated and identified as anti‐HCV compounds, their IC50 being 8.8, 7.2, 4.6 and 16.4 μg/mL, respectively. However, glycyrrhizin, the major constituent of G. uralensis, and its monoammonium salt, showed only marginal anti‐HCV activity. It was also found that licochalcone A and glabridin, known to be exclusive constituents of G. inflata and G. glabra, respectively, did have anti‐HCV activity, their IC50 being 2.5 and 6.2 μg/mL, respectively. Another chalcone, isoliquiritigenin, also showed anti‐HCV activity, with an IC50 of 3.7 μg/mL. Time‐of‐addition analysis revealed that all Glycyrrhiza‐derived anti‐HCV compounds tested in this study act at the post‐entry step. In conclusion, the present results suggest that glycycoumarin, glycyrin, glycyrol and liquiritigenin isolated from G. uralensis, as well as isoliquiritigenin, licochalcone A and glabridin, would be good candidates for seed compounds to develop antivirals against HCV. 相似文献
14.
Tao Guo Rongjiao Xia Tingting Liu Feng Peng Xuemei Tang Qing Zhou Hui Luo Wei Xue 《化学与生物多样性》2020,17(4)
A series of novel chalcone malonate derivatives were synthesized and their antibacterial and antiviral activities were evaluated. All target compounds were characterized by spectral data. The results of antimicrobial bioassay showed that one compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(3‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), with an EC50 value of 10.2 μg/mL, which is significantly superior to bismerthiazol (71.7 μg/mL) and thiodiazole copper (97.8 μg/mL). At the same time, the mechanism of two compounds was confirmed by scanning electron microscopy. In addition, another compound (diethyl [3‐(naphthalen‐2‐yl)‐1‐(4‐nitrophenyl)‐3‐oxopropyl]propanedioate) showed significant curative activity to tobacco mosaic virus, with a value of 74.3 %, which was superior to 53.3 % of ningnanmycin. The results of microscale thermophoresis also showed that the Kd value of the combination of two compounds with the coat protein of tobacco mosaic virus was 0.211 and 0.166 μmol/L, which was better than 0.596 μmol/L of ningnanmycin. At the same time, the molecular docking of two compounds with tobacco mosaic virus‐coat protein shows that the compound is well embedded in the pocket between the two subunits of tobacco mosaic virus‐coat protein. These results show that chalcone derivatives containing malonate group can be considered as activators in the design of antibacterial and antiviral agents. 相似文献
15.
Suratno Lulut Ratnoglik Chie Aoki Pratiwi Sudarmono Mari Komoto Lin Deng Ikuo Shoji Hiroyuki Fuchino Nobuo Kawahara Hak Hotta 《Microbiology and immunology》2014,58(3):188-194
The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo‐Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n‐hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti‐HCV activities with 50%‐inhibitory concentrations (IC50) of 20.6, 6.1, and 6.6 μg/mL, respectively. Bioactivity‐guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti‐HCV compound present in the extracts (IC50 = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti‐HCV activity (IC50 = 0.2 μg/mL). The 50%‐cytotoxic concentrations (CC50) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 μg/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti‐HCV activities. Time‐of‐addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post‐entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV. 相似文献
16.
Lauren E. Seber Kasinger Matthew W. Dent Garima Mahajan Krystal Teasley Hamorsky Nobuyuki Matoba 《Plant biotechnology journal》2019,17(8):1646-1656
The discovery of broadly neutralizing antibodies (bNAbs) has been a major step towards better prophylactic and therapeutic agents against human immunodeficiency virus type 1 (HIV‐1). However, effective therapy will likely require a combination of anti‐HIV agents to avoid viral evasion. One possible solution to this problem is the creation of bispecific molecules that can concurrently target two vulnerable sites providing synergistic inhibitory effects. Here, we describe the production in plants and anti‐HIV activity of a novel bispecific fusion protein consisting of the antigen‐binding fragment (Fab) of the CD4 binding site‐specific bNAb VRC01 and the antiviral lectin Avaren, which targets the glycan shield of the HIV‐1 envelope (VRC01Fab‐Avaren). This combination was justified by a preliminary experiment demonstrating the synergistic HIV‐1 neutralization activity of VRC01 and Fc‐fused Avaren dimer (Avaren‐Fc). Using the GENEWARE® tobacco mosaic virus vector, VRC01Fab‐Avaren was expressed in Nicotiana benthamiana and purified using a three‐step chromatography procedure. Surface plasmon resonance and ELISA demonstrated that both the Avaren and VRC01Fab moieties retain their individual binding specificities. VRC01Fab‐Avaren demonstrated enhanced neutralizing activity against representative HIV‐1 strains from A, B and C clades, compared to equimolar combinations of VRC01Fab and Avaren. Notably, VRC01Fab‐Avaren showed significantly stronger neutralizing effects than the bivalent parent molecules VRC01 IgG and Avaren‐Fc, with IC50 values ranging from 48 to 310 pm . These results support the continued development of bispecific anti‐HIV proteins based on Avaren and bNAbs, to which plant‐based transient overexpression systems will provide an efficient protein engineering and production platform. 相似文献
17.
Doss M Ruchala P Tecle T Gantz D Verma A Hartshorn A Crouch EC Luong H Micewicz ED Lehrer RI Hartshorn KL 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(6):2759-2768
θ-Defensins are cyclic octadecapeptides found in nonhuman primates whose broad antiviral spectrum includes HIV-1, HSV-1, severe acute respiratory syndrome coronavirus, and influenza A virus (IAV). We previously reported that synthetic θ-defensins called retrocyclins can neutralize and aggregate various strains of IAV and increase IAV uptake by neutrophils. This study describes two families of peptides, hapivirins and diprovirins, whose design was inspired by retrocyclins. The goal was to develop smaller partially cyclic peptides that retain the antiviral activity of retrocyclins, while being easier to synthesize. The novel peptides also allowed for systemic substitution of key residues to evaluate the role of charge or hydrophobicity on antiviral activity. Seventy-two hapivirin or diprovirin peptides are described in this work, including several whose anti-IAV activity equals or exceeds that of normal α- or θ-defensins. Some of these also had strong antibacterial and antifungal activity. These new peptides were active against H3N2 and H1N1 strains of IAV. Structural features imparting strong antiviral activity were identified through iterative cycles of synthesis and testing. Our findings show the importance of hydrophobic residues for antiviral activity and show that pegylation, which often increases a peptide's serum t(1/2) in vivo, can increase the antiviral activity of DpVs. The new peptides acted at an early phase of viral infection, and, when combined with pulmonary surfactant protein D, their antiviral effects were additive. The peptides strongly increased neutrophil and macrophage uptake of IAV, while inhibiting monocyte cytokine generation. Development of modified θ-defensin analogs provides an approach for creating novel antiviral agents for IAV infections. 相似文献
18.
H. WAYNE POLLEY ALBERT B. FRANK† JOAQUIN SANABRIA‡ REBECCA L. PHILLIPS† 《Global Change Biology》2008,14(7):1620-1632
The annual carbon (C) budget of grasslands is highly dynamic, dependent on grazing history and on effects of interannual variability (IAV) in climate on carbon dioxide (CO2) fluxes. Variability in climatic drivers may directly affect fluxes, but also may indirectly affect fluxes by altering the response of the biota to the environment, an effect termed ‘functional change’. We measured net ecosystem exchange of CO2 (NEE) and its diurnal components, daytime ecosystem CO2 exchange (PD) and night‐time respiration (RE), on grazed and ungrazed mixed‐grass prairie in North Dakota, USA, for five growing seasons. Our primary objective was to determine how climatic anomalies influence variability in CO2 exchange. We used regression analysis to distinguish direct effects of IAV in climate on fluxes from functional change. Functional change was quantified as the improvement in regression on fitting a model in which slopes of flux–climate relationships vary among years rather than remain invariant. Functional change and direct effects of climatic variation together explained about 20% of variance in weekly means of NEE, PD, and RE. Functional change accounted for more than twice the variance in fluxes of direct effects of climatic variability. Grazing did not consistently influence the contribution of functional change to flux variability, but altered which environmental variable best explained year‐to‐year differences in flux–climate slopes, reduced IAV in seasonal means of fluxes, lessened the strength of flux–climate correlations, and increased NEE by reducing RE relatively more than PD. Most of these trends are consistent with the interpretation that grazing reduced the influence of plants on ecosystem fluxes. Because relationships between weekly values of fluxes and climatic regulators changed annually, year‐to‐year differences in the C balance of these ecosystems cannot be predicted from knowledge of IAV in climate alone. 相似文献
19.
Roberta Tardugno Gilda Giancotti Tine De Burghgraeve Leen Delang Johan Neyts Pieter Leyssen Andrea Brancale Marcella Bassetto 《Bioorganic & medicinal chemistry》2018,26(4):869-874
Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells. Structure-activity relationships were elucidated for the original scaffolds, and different novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these promising novel structures as antiviral agents against Chikungunya virus. 相似文献
20.
Shu‐Ting Chung Yi‐Ting Huang Hsin‐Yi Hsiung Wen‐Hsin Huang Chen‐Wen Yao An‐Rong Lee 《化学与生物多样性》2015,12(4):685-696
A series of novel isoflavonoids were synthesized based on structural modifications of daidzein, an active ingredient of traditional Chinese medicine (TCM) and evaluated for their anti‐influenza activity, in vitro, against H1N1 Tamiflu‐resistant (H1N1 TR) virus in the MDCK cell line. Among them, 4‐oxo‐4H‐1‐benzopyran‐8‐carbaldehydes 11a – 11g were most promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent. 3‐(4‐Bromophenyl)‐7‐hydroxy‐4‐oxo‐4H‐1‐benzopyran‐8‐carboxaldehyde ( 11c ) displayed the best inhibitory activity (EC50, 29.0 μM ) and selectivity index (SI>10.3). Analysis of the structure? activity relationships (SAR) indicated that both the non‐naturally‐occurring Br‐substituted B‐ring and appropriate CHO and OH groups on the A‐ring might be critical for the activity and selectivity against H1N1 TR influenza viruses. 相似文献