Study of the antiviral activity of the nucleoside analogue 2-(beta-D-ribofuranosyl)-5-amino-1,2,4-triazine-3(2H)-one against Epstein-Barr virus

2015 ◽  
Author(s):  
Anna Golovan ◽  
Kristina Naumenko ◽  
Galina Baranova ◽  
Svitlana Zagorodnya
Keyword(s):  
Antiviral Activity ◽  
Nucleoside Analogue ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Inhibition of Herpesvirus Replication by Hexadecyloxypropyl Esters of Purine- and Pyrimidine-Based Phosphonomethoxyethyl Nucleoside Phosphonates

2008 ◽  
Vol 52 (12) ◽  
pp. 4326-4330 ◽  
Author(s):  
Mark N. Prichard ◽  
Caroll B. Hartline ◽  
Emma A. Harden ◽  
Shannon L. Daily ◽  
James R. Beadle ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Hiv Infections ◽  
Barr Virus ◽  
Immunodeficiency Virus ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Ester Prodrugs

ABSTRACT Patients infected with human immunodeficiency virus (HIV) often suffer from herpesvirus infections as a result of immunosuppression. These infections can occur while patients are receiving antiretroviral therapy, and additional drugs required to treat their infection can adversely affect compliance. It would be useful to have antivirals with a broader spectrum of activity that included both HIV and the herpesviruses. We reported previously that alkoxyalkyl ester prodrugs of cidofovir are up to 3 orders of magnitude more active against herpesvirus replication and may be less toxic than the unmodified drug. To determine if this strategy would be effective for certain phosphonomethoxyethyl nucleoside phosphonates which are also active against HIV infections, the hexadecyloxypropyl (HDP) esters of 1-(phosphonomethoxyethyl)-cytosine, 1-(phosphonomethoxyethyl)-5-bromo-cytosine (PME-5BrC), 1-(phosphonomethoxyethyl)-5-fluoro-cytosine, 9-(phosphonomethoxyethyl)-2,6-diaminopurine (PME-DAP), and 9-(phosphonomethoxyethyl)-2-amino-6-cyclopropylaminopurine (PME-cPrDAP) were evaluated for activity against herpesvirus replication. The HDP esters were substantially more active than the unmodified acyclic nucleoside phosphonates, indicating that esterification with alkoxyalkyl groups increases the antiviral activity of many acyclic nucleoside phosphonates. The most interesting compounds included HDP-PME-cPrDAP and HDP-PME-DAP, which were 12- to 43-fold more active than the parent nucleoside phosphonates against herpes simplex virus and cytomegalovirus, and HDP-PME-cPrDAP and HDP-PME-5BrC which were especially active against Epstein-Barr virus. The results presented here indicate that HDP-esterified acyclic nucleoside phosphonates with antiviral activity against HIV also inhibit the replication of some herpesviruses and can extend the spectrum of activity for these compounds.

scholarly journals Antiherpesvirus Activities of Two Novel 4′-Thiothymidine Derivatives, KAY-2-41 and KAH-39-149, Are Dependent on Viral and Cellular Thymidine Kinases

2014 ◽  
Vol 58 (8) ◽  
pp. 4328-4340 ◽  
Author(s):  
Natacha Coen ◽  
Sophie Duraffour ◽  
Kazuhiro Haraguchi ◽  
Jan Balzarini ◽  
Joost J. van den Oord ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients. Furthermore, effective antiviral therapies against gammaherpesvirus-associated diseases are lacking. Here, we present two thiothymidine derivatives, KAY-2-41 and KAH-39-149, with different spectra of antiviral activity from those of the reference antiherpetic drugs, showing inhibitory activities against herpes simplex virus, varicella-zoster virus (VZV), and particularly against Epstein-Barr virus, with high selectivityin vitro. While KAY-2-41- and KAH-39-149-resistant herpesviruses were found to harbor mutations in the viral thymidine kinase (TK), these mutations conferred only low levels of resistance to these drugs but high levels to other TK-dependent drugs. Also, antiviral assays in HeLa TK-deficient cells showed a lack of KAY-2-41 and KAH-39-149 activities against herpes simplex virus 1 (HSV-1) and HSV-2 TK-deficient mutants. Furthermore, enzymatic TK assays showed the ability of HSV-1 TK, VZV TK, and cellular TK1 and TK2 to recognize and phosphorylate KAY-2-41 and KAH-39-149. These results demonstrate that the compounds depend on both viral and host TKs to exert antiviral activity. Additionally, the antiviral efficacy of KAH-39-149 proved to be superior to that of KAY-2-41 in a mouse model of gammaherpesvirus infection, highlighting the potential of this class of antiviral agents for further development as selective therapeutics against Epstein-Barr virus.

scholarly journals ВИВЧЕННЯ ПРОТИВІРУСНОЇ АКТИВНОСТІ ТАБЛЕТОК АЛЬТАБОР

2015 ◽  
Author(s):  
С. Л. Рибалко ◽  
Т. В. Крутських ◽  
А. С. Шаламай
Keyword(s):  
Antiviral Activity ◽  
Infectious Diseases ◽  
Epstein Barr Virus ◽  
Therapeutic Index ◽  
The Body ◽  
Herpes Viruses ◽  
Barr Virus ◽  
The World ◽  
Influenza Activity ◽  
Epstein Barr

<p><strong>STUDY OF ANTIVIRAL ACTIVITY OF TABLETS ALTABOR </strong></p><p><strong>S.L. Rybalko<sup>1</sup>, </strong><strong>Т</strong><strong>.V. </strong><strong>К</strong><strong>rutskikh<sup>2</sup>, </strong><strong>А</strong><strong>.S. Shalamay<sup>3</sup></strong></p><p><sup>1</sup>L.V.Gromashevsky Institute of epidemiology and infectious diseases Academy of Medical Science of Ukraine, Kyiv</p><p><sup>2</sup>National Pharmaceutical University, Kharkiv</p><p><sup>3</sup>JSC SIC "Borshchahivka CPP", Kyiv</p><p><strong>Summary:</strong> studied antiviral activity of tablets Altabor. Determined that the drug has antiviral activity and inhibits the reproduction of Epstein-Barr virus.</p><p><strong>Key words:</strong> altabor, antiviral activity, influenza, Epstein-Barr virus.</p><p><strong>Introduction.</strong> Among all infectious diseases flu and SARS took first place in frequency and the number of cases in the world and account for 95%. According to WHO influenza and flu-like illness in the world is sick 5 - 30 % of the population is 500 million people. For 400 years the world's recorded over 100 epidemics of influenza pandemics and 18, which bring it with them tens of millions of lives. Today, global losses from influenza epidemics is much inferior to the scale of past pandemics due to the possibilities of modern diagnosis of the virus , the availability of antiviral and antibacterial drugs and improving health services. But the problem of treatment of disease really matter remains relevant.</p><p>Against the background of acute viral infections of herpes viruses can be said not, but no less threatening. Herpes was first fixed in a thousand years BC, but the problem that attracts attention, was only in the 20th century after the emergence of HIV. Today open 80 more members of the family of herpes viruses, of which 8 types pathogenic to man. One of the pathogenic types are Epstein-Barr virus, which, according to research antibodies detected in 95% of the population. At this time this virus play an important role in the formation of cancer cells in the body that causes the need for increasing attention from the medical and pharmaceutical community.</p><p>Create antiviral agents is one of the most difficult tasks chemotherapy infections. The reason is that viruses containing RNA and DNA components are obligate intracellular parasites. In the process of viral replication is mainly used machine biosynthesis microorganism cells, modifying its outstanding manner. In this regard, it is very difficult to find selective operating means which would killed viruses without damaging the cells are "master". However, in recent years, certain antiviral drugs that possess outstanding selective action against the infected cells and suppress the virus replicative cycle. One of these drugs is original domestic product - Altabor tablets.</p><p><strong>Methods.</strong> Antiviral activity of Altabor tablets studied in models in vitro. To determine influenza activity using dog kidney cell culture .The influence of tablets Altabor on virus Epstein-Barr conducted in the system Raji cells infected with the said virus.</p><p><strong>Results and discussion</strong>. Altabor tablets influenza activity based on the inhibition of viral neuraminidase, an enzyme responsible for viral virion ability to penetrate the host cell and leave it after reproduction. Analyzing these data, it should be noted that tablets Altabor actively inhibit the reproduction of the influenza virus in doses from 100 mg/ml to 6.75 ug/ml 7.5-3.0 lg ID50, which indicates a strong flu drug activity. As for the study of the effect of tablets on Altabor Epstein-Barr virus, the maximum tolerated concentration was 750 mg/ml. Determined that the minimum active concentration for the drug was 0.1 mg/ml. Based on the value of the minimum and maximum tolerated concentration of active therapeutic index of tablets Altabor established at 5000, indicating a pronounced effects on reproduction of the virus.</p><p><strong>Conclusions.</strong> Result of studies on the antiviral activity of tablets Altabor found that the preparation has flu activity. Also, the drug inhibits the reproduction of Epstein-Barr virus, as evidenced therapeutic index of tablets Altabor set at 5000.</p>

scholarly journals The Latent Membrane Protein 1 of Epstein-Barr Virus Establishes an Antiviral State via Induction of Interferon-stimulated Genes

2004 ◽  
Vol 279 (44) ◽  
pp. 46335-46342 ◽  
Author(s):  
Jun Zhang ◽  
Subash C. Das ◽  
Catherine Kotalik ◽  
Asit K. Pattnaik ◽  
Luwen Zhang
Keyword(s):  
Membrane Protein ◽  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Antiviral Effect ◽  
Latent Membrane Protein ◽  
Lytic Replication ◽  
Latent Membrane Protein 1 ◽  
Antiviral State ◽  
Barr Virus ◽  
Epstein Barr

Epstein-Barr virus (EBV) infection is associated with several human cancers. Latent membrane protein 1 (LMP-1) is one of the key viral proteins required for transformation of primary B cellsin vitroand establishment of EBV latency. In this report, we show that LMP-1 is able to induce the expression of several interferon (IFN)-stimulated genes (ISGs) with antiviral properties such as 2′-5′ oligoadenylate synthetase (OAS), stimulatedtrans-acting factor of 50 kDa (STAF-50), and ISG-15. LMP-1 inhibits vesicular stomatitis virus (VSV) replication at low multiplicity of infection (0.1 pfu/cell). The antiviral effect of LMP-1 is associated with the ability of LMP-1 to induce ISGs; an LMP-1 mutant that cannot induce ISGs fails to induce an antiviral state. High levels of ISGs are expressed in EBV latency cells in which LMP-1 is expressed. EBV latency cells have antiviral activity that inhibits replication of superinfecting VSV. The antiviral activity of LMP-1 is apparently not related to IFN production in our experimental systems. In addition, EBV latency is responsive to viral superinfection: LMP-1 is induced and EBV latency is disrupted by EBV lytic replication during VSV superinfection of EBV latency cells. These data suggest that LMP-1 has antiviral effect, which may be an intrinsic part of EBV latency program to assist the establishment and/or maintenance of EBV latency.

scholarly journals Antiviral Activity of Extracts from Wild Grasses against Epstein-Barr Virus and Induction of Apoptosis in EBV-positive Lymphoblastoid Cells

2017 ◽  
Author(s):  
Svitlana Zagorodnya ◽  
Anna Golovan ◽  
Galina Baranova ◽  
Svitlana Rybalko ◽  
Lyubov Zelena ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Lymphoblastoid Cells ◽  
Barr Virus ◽  
Strong Antiviral Activity ◽  
Induction Of Apoptosis ◽  
Epstein Barr
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