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担子菌提取物和腐殖化合物物质对人类免疫缺陷病毒(逆转录病毒科:正逆转录亚科:慢病毒属:人类免疫缺陷病毒1型)和单纯疱疹病毒(疱疹病毒科:单纯疱疹病毒属:人类α疱疹病毒1型)的抗病毒活性

[Antiviral activity of extracts of basidiomycetes and humic compounds substances against Human Immunodeficiency Virus (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus 1) and Herpes Simplex Virus (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1)].

作者信息

Nosik D N, Nosik N N, Teplyakova T V, Lobach O A, Kiseleva I A, Kondrashina N G, Bochkova M S, Ananko G G

机构信息

The D.I. Ivanovsky Institute of Virology FSBI «National Research Center of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya» of the Ministry of Health of Russia.

FBU State Research Center of Virology and Biotechnology «Vector» of Rospotrebnadzor.

出版信息

Vopr Virusol. 2020 Nov 14;65(5):276-283. doi: 10.36233/0507-4088-2020-65-5-4.

Abstract

INTRODUCTION

One of the most urgent problem of modern medicine is the fight against the disease caused by the Human Immunodeficiency Virus (HIV) - HIV infection. The chemical compounds have improved the situation for infected people, but they are toxic, disrupt the metabolism and cannot eliminate the integrated virus from the body. The emergence of resistant HIV strains makes these treatments ineffective. Often, the death of HIV-infected people occurs as a result of the development of opportunistic infections caused by viruses of the Herpesviridae family. Therefore, the search for new therapeutic and preventive drugs that are less toxic and active against several viruses at the same time is relevant. Basidiomycetes, higher fungi, are a source of medicinal compounds that have antimicrobial properties, as well as antiviral ones. Humic compounds (HS) of various nature also have antiviral activity.The aim of the study was to obtain nontoxic compounds from the basidiomycete Inonotus obliquus and humic compounds from brown coals and to test their activity against viruses that are pathogenic to humans: HIV and Herpes Simplex Virus (HSV).

MATERIAL AND METHODS

The antiviral activity of melanin extracts obtained from the culture of the chaga fungus Inonotus obliquus and HS from the brown coal of the Kansko-Achinsk Deposit was studied using a model of MT-4 lymphoblastoid cells infected with HIV type 1 (HIV-1) strains and a monolayer culture of Vero cells infected with HSV type 1 (HSV-1) using virological and statistical research methods.

RESULTS AND DISCUSSION

It was found that all the studied compounds did not have a cytotoxic effect on cells at a concentration of 100 mcg/ml. It was shown that extracts of basidiomycetes and HS have antiviral activity against HIV-1 and HSV-1. EC 50 (50%-effective concentration) for HIV-1 was 3.7-5.0 mcg/ml, selectivity index 28-35. Antiherpetic activity was detected at a dose of 50-100 mcg/ml. The antiviral effectiveness of melanin compounds was established both in the «preventive» (2 hours before cell infection) and in the «therapeutic» regimen of drug administration, both for HIV-1 and HSV-1. The presence of antiviral activity of melanin and HS in relation to the RNA-containing HIV-1 virus and DNA-containing HSV-1 virus in our study coincides with the results of a number of authors in relation to influenza viruses, herpes virus, HIV, hepatitis B virus, Coxsackievirus, smallpox vaccine virus, which suggests that the type of nucleic acid in the virus does not play a fundamental role in the antiviral action of these drugs. It is also clear that HS is effective against both enveloped and non-enveloped viruses.

CONCLUSION

In general, it can be concluded that melanin and humic compounds are characterized by low toxicity in the presence of both virucidal and antiviral activity. This allows us to consider the studied compounds as the basis for creating safe medicines that are effective against pathogens of various viral infections.

摘要

引言

现代医学最紧迫的问题之一是对抗由人类免疫缺陷病毒(HIV)引起的疾病——HIV感染。化学化合物改善了感染者的状况,但它们有毒性,会扰乱新陈代谢,且无法从体内清除整合的病毒。耐药HIV毒株的出现使这些治疗方法失效。通常,HIV感染者的死亡是由疱疹病毒科病毒引起的机会性感染所致。因此,寻找毒性较小且能同时对抗多种病毒的新型治疗和预防药物具有重要意义。担子菌,即高等真菌,是具有抗菌特性以及抗病毒特性的药用化合物的来源。各种性质的腐殖质化合物(HS)也具有抗病毒活性。本研究的目的是从担子菌桦褐孔菌中获得无毒化合物,并从褐煤中获得腐殖质化合物,然后测试它们对人类致病病毒:HIV和单纯疱疹病毒(HSV)的活性。

材料与方法

使用病毒学和统计学研究方法,以感染1型HIV(HIV-1)毒株的MT-4淋巴母细胞模型和感染1型HSV(HSV-1)的Vero细胞单层培养物为对象,研究从桦褐孔菌培养物中获得的黑色素提取物和堪斯克-阿钦斯克矿床褐煤中的HS的抗病毒活性。

结果与讨论

发现在浓度为100微克/毫升时,所有研究的化合物对细胞均无细胞毒性作用。结果表明,担子菌提取物和HS对HIV-1和HSV-1具有抗病毒活性。HIV-1的半数有效浓度(EC50)为3.7-5.0微克/毫升,选择性指数为28-35。在剂量为50-100微克/毫升时检测到抗疱疹活性。黑色素化合物的抗病毒有效性在药物给药的“预防”(细胞感染前2小时)和“治疗”方案中均得到证实,对HIV-1和HSV-1均有效。在我们的研究中,黑色素和HS对含RNA的HIV-1病毒和含DNA的HSV-1病毒具有抗病毒活性,这与许多作者关于流感病毒、疱疹病毒、HIV、乙型肝炎病毒、柯萨奇病毒、天花疫苗病毒的研究结果一致,这表明病毒中的核酸类型在这些药物的抗病毒作用中不起根本作用。同样明显的是,HS对包膜病毒和非包膜病毒均有效。

结论

总体而言,可以得出结论,黑色素和腐殖质化合物在具有杀病毒和抗病毒活性的同时具有低毒性。这使我们能够将所研究的化合物视为开发对各种病毒感染病原体有效的安全药物的基础。

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