Antiviral activities and putative identification of compounds in microbial extracts from the Hawaiian coastal waters

Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1), vesicular stomatitis virus (VSV), vaccinia virus and poliovirus type one (poliovirus-1) using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5α(H),17α(H),(20R)-beta-acetoxyergost-8(14)-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies.     

Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro

Much attention is being devoted to the potential of marine sulfated polysaccharides as antiviral agents in preventing COVID-19. In this study, sulfated fucoidan and crude polysaccharides, extracted from six seaweed species (Undaria pinnatifida sporophyll, Laminaria japonica, Hizikia fusiforme, Sargassum horneri, Codium fragile, Porphyra tenera) and Haliotis discus hannai (abalone viscera), were screened for their inhibitory activity against SARS-CoV-2 virus entry. Most of them showed significant antiviral activities at an IC50 of 12~289 μg/mL against SARS-CoV-2 pseudovirus in HEK293/ACE2, except for P. tenera (IC50 > 1000 μg/mL). The crude polysaccharide of S. horneri showed the strongest antiviral activity, with an IC50 of 12 μg/mL, to prevent COVID-19 entry, and abalone viscera and H. fusiforme could also inhibit SARS-CoV-2 infection with an IC50 of 33 μg/mL and 47 μg/mL, respectively. The common properties of these crude polysaccharides, which have strong antiviral activity, are high molecular weight (>800 kDa), high total carbohydrate (62.7~99.1%), high fucose content (37.3~66.2%), and highly branched polysaccharides. These results indicated that the crude polysaccharides from seaweeds and abalone viscera can effectively inhibit SARS-CoV-2 entry.     

Evaluation of Antiviral Effect against SARS-CoV-2 Propagation by Crude Polysaccharides from Seaweed and Abalone Viscera In Vitro

Crude polysaccharides, extracted from two seaweed species (Hizikia fusiforme and Sargassum horneri) and Haliotis discus hannai (abalone) viscera, were evaluated for their inhibitory effect against SARS-CoV-2 propagation. Plaque titration revealed that these crude polysaccharides efficiently inhibited SARS-CoV-2 propagation with IC₅₀ values ranging from 0.35 to 4.37 μg/mL. The crude polysaccharide of H. fusiforme showed the strongest antiviral effect, with IC₅₀ of 0.35 μg/mL, followed by S. horneri and abalone viscera with IC₅₀ of 0.56 and 4.37 μg/mL, respectively. In addition, immunofluorescence assay, western blot, and quantitative RT-PCR analysis verified that these polysaccharides could inhibit SARS-CoV-2 replication. In Vero E6 cells, treatment with these crude polysaccharides before or after viral infection strongly inhibited the expression level of SARS-CoV-2 spikes, nucleocapsid proteins, and RNA copies of RNA-dependent RNA-polymerase and nucleocapsid. These results show that these crude marine polysaccharides effectively inhibit SARS-CoV-2 propagation by interference with viral entry.     

Nutritional and Chemical Composition and Antiviral Activity of Cultivated Seaweed Sargassum naozhouense Tseng et Lu

Sargassum naozhouense is a brown seaweed used in folk medicine and applied for thousands of years in Zhanjiang, Guangdong province, China. This study is the first time to investigate its chemical composition and antiviral activity. On the dry weight basis, this seaweed was constituted of ca. 35.18% ash, 11.20% protein, 1.06% lipid and 47.73% total carbohydrate, and the main carbohydrate was water-soluble polysaccharide. The protein analysis indicated the presence of essential amino acids, which accounted for 36.35% of the protein. The most abundant fatty acids were C14:0, C16:0, C18:1 and C20:4. The ash fraction analysis indicated that essential minerals and trace elements, such as Fe, Zn and Cu, were present in the seaweed. IR analysis revealed that polysaccharides from cultivated S. naozhouense may be alginates and fucoidan. The polysaccharides possessed strong antiviral activity against HSV-1 in vitro with EC₅₀ of 8.92 μg/mL. These results demonstrated cultivated S. naozhouense has a potential for its use in functional foods and antiviral new drugs.     

Bioactive Compounds and Health-Promoting Properties of Berry Fruits: A Review

This study characterizes biologically active compounds of berry fruits, including non-nutritive compounds such as phenolic compounds, including anthocyanins, phenolic acids, stilbens and tannins, as well as nutritive compounds such as carotenoids and vitamin C. It discusses the biological activity of those compounds, in particular their antioxidant properties and the resulting health benefits.     

The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview

Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure–activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail.     

Antiviral activities of sulfated polysaccharides isolated from Sphaerococcus coronopifolius (Rhodophytha, Gigartinales) and Boergeseniella thuyoides (Rhodophyta, Ceramiales)

Water-soluble sulfated polysaccharides isolated from two red algae Sphaerococcus coronopifolius (Gigartinales, Sphaerococcaceae) and Boergeseniella thuyoides (Ceramiales, Rhodomelaceae) collected on the coast of Morocco inhibited in vitro replication of the Human Immunodeficiency Virus (HIV) at 12.5 μg/mL. In addition, polysaccharides were capable of inhibiting the in vitro replication of Herpes simplex virus type 1 (HSV-1) on Vero cells values of EC₅₀ of 4.1 and 17.2 μg/mL, respectively. The adsorption step of HSV-1 to the host cell seems to be the specific target for polysaccharide action. While for HIV-1, these results suggest a direct inhibitory effect on HIV-1 replication by controlling the appearance of the new generations of virus and potential virucidal effect. The polysaccharides from S. coronopifolius (PSC) and B. thuyoides (PBT) were composed of galactose, 3,6-anhydrogalactose, uronics acids, sulfate in ratios of 33.1, 11.0, 7.7 and 24.0% (w/w) and 25.4, 16.0, 3.2, 7.6% (w/w), respectively.     

茶多糖对肉仔鸡免疫功能和抗氧化能力的影响

在AA肉鸡的饮水中分别加入0%、0.2%和0.4%的茶多糖,研究其对肉仔鸡免疫功能和抗氧化能力的影响。试验结果表明,茶多糖能显著促进肉仔鸡胸腺的生长发育(P<0.05),可以明显升高血清中免疫球蛋白IgG的含量(P<0.05),提高T-淋巴细胞数和淋巴细胞转化率(P<0.05),增强白细胞吞噬功能(P<0.05),但对法氏囊的生长发育没有明显作用;同时,茶多糖能显著提高肉仔鸡血清中SOD活力(P<0.05)、GSH-Px活力(P<0.05)和CAT活力(P<0.05),并能明显降低血清中MDA含量(P<0.05)。     

Immunomodulatory Activity In Vitro and In Vivo of a Sulfated Polysaccharide with Novel Structure from the Green Alga Ulva conglobata Kjellman

Algae accumulate large amounts of polysaccharides in their cell walls or intercellular regions. Polysaccharides from algae possess high potential as promising candidates for marine drug development. In this study, a sulfated polysaccharide, UCP, from the green alga Ulva conglobata Kjellman was obtained by water extraction, anion-exchange, and size-exclusion chromatography purification, and its structure was characterized by a combination of chemical and spectroscopic methods. UCP mainly consisted of →4)-α/β-l-Rhap-(1→, →4)-β-d-Xylp-(1→ and →4)-β-d-GlcAp-(1→ residues. Sulfate ester groups were substituted mainly at C-3 of →4)-l-Rhap-(1→ and C-2 of →4)-β-d-Xylp-(1→. Partial glycosylation was at C-2 of →4)-α-l-Rhap-(1→ residues. UCP possessed a potent immunomodulatory effect in vitro, evaluated by the assays of lymphocyte proliferation and macrophage phagocytosis. The immunomodulatory activity of UCP in vivo was further investigated using immunosuppressive mice induced by cyclophosphamide. The results showed that UCP markedly increased the spleen and thymus indexes and ameliorated the cyclophosphamide-induced damage to the spleen and thymus. UCP could increase the levels of white blood cells, lymphocytes, and platelets, and improve the hematopoietic inhibition caused by cyclophosphamide. Moreover, UCP significantly promoted the secretions of the immunoglobulin (Ig)G, IgE, and IgM. The data demonstrated that UCP is a novel sulfated polysaccharide and may be a promising immunomodulatory agent.     

Semi-Synthesis,Cytotoxic Evaluation,and Structure—Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity

Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2–16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure–activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC₅₀ value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1–GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.     

绿茶和红茶多酚类化合物的抗病毒活性在新型冠状病毒肺炎预防和治疗中的应用

新型冠状病毒SARS-CoV-2或nCoV的迅速传播,已引起世界各国的高度重视并采取严格的预防和隔离措施.这个新的单链RNA冠状病毒通过唾液和鼻腔分泌物传播.鉴于新型冠状病毒感染病例数日益增多,美国食品药品监督管理局(FDA)已授权紧急使用瑞德西韦(Remdesivir)治疗,但至今仍然没有任何一种药物获批准用于治疗C...     

Biological Properties and Health-Promoting Functions of Laminarin: A Comprehensive Review of Preclinical and Clinical Studies

Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or β-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.     

Optimized Degradation and Inhibition of α-glucosidase Activity by Gracilaria lemaneiformis Polysaccharide and Its Production In Vitro

Gracilaria lemaneiformis polysaccharide (GLP) exhibits good physiological activities, and it is more beneficial as it is degraded. After its degradation by hydrogen peroxide combined with vitamin C (H₂O₂-Vc) and optimized by Box–Behnken Design (BBD), a new product of GLP-HV will be generated. While using GLP as control, two products of GLP-H (H₂O₂-treated) and GLP-V (Vc-treated) were also produced. These products chemical characteristics (total sugar content, molecular weight, monosaccharide composition, UV spectrum, morphological structure, and hypolipidemic activity in vitro) were assessed. The results showed that the optimal conditions for H₂O₂-Vc degradation were as follows: H₂O₂-Vc concentration was 18.7 mM, reaction time was 0.5 h, and reaction temperature was 56 °C. The total sugar content of GLP and its degradation products (GLP-HV, GLP-H and GLP-V) were more than 97%, and their monosaccharides are mainly glucose and galactose. The SEM analysis demonstrated that H₂O₂-Vc made the structure loose and broken. Moreover, GLP, GLP-HV, GLP-H, and GLP-V had significantly inhibition effect on α-glucosidase, and their IC₅₀ value were 3.957, 0.265, 1.651, and 1.923 mg/mL, respectively. GLP-HV had the best inhibition effect on α-glucosidase in a dose-dependent manner, which was the mixed type of competitive and non-competitive. It had a certain quenching effect on fluorescence of α-glucosidase, which may be dynamic quenching.     

甜菜对土壤肥力及酶活性影响的初步分析

研究结果表明，在被测定的１２种甜菜土壤养分含量中，有１０种养分含量低于对照（麦地）．其中，碱解氮，有效镁和有效锰的差异较大，其差值分别为２６ｐｐｍ、１１．５ｐｐｍ和７．４ｐｐｍ，其余差异不大；在甜菜营养生长期内，分别测定了甜菜与对照土壤的微生物总量、细菌、放线菌和真菌的数量及消长动态；土壤碱解氮含量和耕层地温对细菌数量有一定的影响；甜菜土壤的３项酶活性均低于同期的对照。在甜菜吸收氮素的高峰期，土壤中脲酶活性亦明显增强，达到１．２２ＮＨ＿３－Ｎｍｇ／ｇ土。在幼苗期至糖分积累期，磷酸酶活性与甜菜苗龄呈正相关关系（ｒ＝０．９２２３￣＊）。     

假眼小绿叶蝉的日飞行活动性及成虫飞行能力的研究

茶树假眼小绿叶蝉（Empoasca vitis Göthe）在早晨和傍晚各有一个飞行活动高峰,早晨的活动高峰时间为6:00~7:00,傍晚的活动高峰时间为16:00~17:00。假眼小绿叶蝉成虫的平均飞行距离、平均飞行时间和平均飞行速度在一天之中不同的时间段下无显著性差异,但雌雄成虫的平均停飞时间在晚上（22:00~23:00）显著增加,在中午（12:00~13:00）雄虫的平均停飞时间显著要长于雌虫。研究结果为假眼小绿叶蝉的生物特征分析和田间防治提供了参考。     

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial,Antidiabetic, Antifungal,Anti-Inflammatory,Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems,and Other Miscellaneous Mechanisms of Action

The review of the 2016–2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016–2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016–2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.     

醋制对黑豆蛋白含量及多肽ACE抑制活性的影响

为考察醋制对黑豆蛋白含量及多肽ACE抑制活性的影响,为对黑豆醋浸过程中蛋白组分及含量变化进行分析,并对相应ACE抑制肽活性进行测定。黑豆经醋浸不同时间后,采用顺序抽提法提取清蛋白、球蛋白、醇溶蛋白和谷蛋白,并采用凯氏定氮法及SDS-PAGE电泳进行定量和定性分析;各蛋白组分经胃蛋白酶水解,经超滤(截留分子量3 k D)后收集滤液,获得多肽组分,RP-HPLC法进行ACE抑制活性评价。结果表明:经醋浸14 d后,黑豆总蛋白含量变化幅度小于±0.5%;清蛋白含量由55.13%(0 d)降低至9.61%(14 d);球蛋白由7.04%(0 d)增加到20.34%(14 d);醇溶蛋白由0.81%(0 d)增加到1.72(14 d);谷蛋白由21.11%(0 d)增加到59.45%(14 d),含量最高。醋浸处理降低了清蛋白源多肽的ACE抑制活性,但提高了球蛋白、醇溶蛋白及谷蛋白多肽的ACE抑制活性,其中,谷蛋白多肽抑制率由18.18%(0 d)增加至37.58%(14 d),抑制活性升高。醋浸可改变黑豆各蛋白组分的含量和对应多肽的ACE抑制活性,其中,谷蛋白含量及其多肽ACE抑制活性均有增加。研究结果表明可进一步采用分离纯化技术从谷蛋白多肽中获得高活性降压肽。     

Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber Eupentacta fraudatrix with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent. Two different mechanisms of glycoside/membrane interactions were discovered. The first one was realized through the pore formation (by cucumariosides A₁ (40) and A₈ (44)), preceded by bonding of the glycosides with membrane sphingomyelin, phospholipids, and cholesterol. Noncovalent intermolecular interactions inside multimolecular membrane complexes and their stoichiometry differed for 40 and 44. The second mechanism was realized by cucumarioside A₂ (59) through the formation of phospholipid and cholesterol clusters in the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were more favorable compared to the glycoside/cholesterol interactions, but the glycoside possessed an agglomerating action towards the cholesterol molecules from the inner membrane leaflet. In silico simulations of the interactions of cucumarioside A₇ (45) with model membrane demonstrated only slight interactions with phospholipid polar heads and the absence of glycoside/cholesterol interactions. This fact correlated well with very low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in good agreement with the corresponding experimental data on hemolytic activity of the investigated compounds in vitro.