Mikrobiol. Z. 2018; 80(5):98-109. Ukrainian.
Anti-Adenoviral Activity of Neoflazid in vitro
Povnitsa O.Yu.1, Biliavska L.O.1, Pankivska Yu.B.1, Naumenko K.S.1,
Zelena L.B.1, Zagorodnya S.D.1, Atamanyuk V.P.2
1Zabolotny Institute of Microbiology and Virology, NAS of Ukraine
154 Akad. Zabolotny Str., Kyiv, 03143, Ukraine
2SMC Ecopharm Ltd.
9-V Stepan Bandera Ave., Kyiv, 04073, Ukraine
More than 70 types of human adenovirus cause various infectious diseases, which in the case of immunodeficiency conditions lead to a high risk of developing a generalized form of a viral infection. The assortment of drugs with anti-adenoviral effect is very limited. High toxicity is the main problem of existing synthetic antiviral drugs. Aim. Study of cytotoxic, virucidal and anti-adenoviral effect of the drug Neoflazid (new substance of Proteflazid with a calibrated content of the active substance), its biologically active substance (BASP) and its synthetic analog (BAS SA). Methods. To determine the cytotoxic, virulicide and anti adenoviral effects of the substances, MTT assay was used. The level of accumulation of the viral nucleic acid in the cells was determined by PCR analysis. The infectious titer of the virus, synthesized in the presence of substances, was determined by cytopathic action on the cells at the end point of the virus breeding, which causes 50 % CPE. Results. The cytotoxic concentration (CC50) in the A 549 cells for the drug Neoflazid, the substances BASP and BAS SA were 10 μg/ml, 76 μg/ml, and 43 μg/ml, respectively. The test substances did not have a pronounced virucidal effect. Titration of the adenovirus synthesized by de novo in the presence of substances revealed an anti-adenoviral property, since the drug Neoflazid, BASP and BAS SA declaimed completely the formation of infectious adenovirus at concentrations of 7.1 μg/ml, 30 μg/ml, and 10 μg/ml, respectively. Conclusions. The drug Neoflazid of SMC Ekopharm (Kyiv, Ukraine), its biologically active substance (BASP) and its synthetic analog of BASP (BAS SA) are able to inhibit the formation of infectious adenovirus, which gives the prospect for appropriate clinical trials.
Keywords: Neoflazid, flavonoids, adenovirus, antiviral activity.
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- Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clinical Microbiology Reviews. 2014; 27(3):441–62. https://doi.org/10.1128/CMR.00116-13
- Hage E, Liebert G, Bergs U, Ganzenmueller T, Heim A. Human mastadenovirus type 70: a novel, multiple recombinant species D mastadenovirus isolated from diarrhoeal faeces of a haematopoietic stem cell transplantation recipient. Journal of Gen Virology. 2015; 96(9):2734–42. https://doi.org/10.1099/vir.0.000196
- Grosso F, Stoilov P, Lingwood C, Brown M, Cochrane A. Suppression of adenovirus replication by cardiotonic steroids. Journal of Virology. 2017; 91(3):1623-39. https://doi.org/10.1128/JVI.01623-16
- Epiphanova NV, Navikova NA. [The role of adenoviruses in the occurrence of acute intestinal infection in children (Analytical Review)] Medial. 2014; 2(12):45-57. Russian.
- Kinchington PR, Romanowski EG, Gordon YJ. Prospects for adenovirus antivirals. Journal of Antimicrobal Chemotherapy. 2005; 55:424-429. https://doi.org/10.1093/jac/dki057
- Lenaerts L, Naesens L. Antiviral therapy for adenovirus infections. Antiviral Res. 2006; 71:172-180. https://doi.org/10.1016/j.antiviral.2006.04.007
- Wold WSM, Toth K. New drug on the horizon for treating adenovirus. Expert Opin Pharmacother. 2015; 16(14):2095–99. https://doi.org/10.1517/14656566.2015.1083975
- Strand M. The discovery of antiviral compounds targeting adenovirus and herpes simplex virus. Assessment of synthetic compounds and natural products. Doctoral thesis, Department of Clinical Microbiology, Virology, Umeå University. 2014.
- De Clercq E. The clinical potential of the acyclic (and cyclic) nucleoside phosphonates: the magic of the phosphonate bond. Biochem Pharmacol. 2011; 82:99–109. https://doi.org/10.1016/j.bcp.2011.03.027
- Naesens L, Lenaerts L, Andrei G, Snoeck R, Van Beers D, Holy A, et al. Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother. 2005; 49(3):1010–16. https://doi.org/10.1128/AAC.49.3.1010-1016.2005
- Lankester AC, Heemskerk B, Claas ECJ, Schilham MW, Beersma MF, Bredius RG, et al. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin. Infect. Dis. 2004; 38(11):1521-25. https://doi.org/10.1086/420817
- Da Silva AC, Kratz JM, Farias FM, Henriques AT, Dos Santos J, Leonel RM., et al. In vitro antiviral activity of marine sponges collected off Brasillian coast. Biol. Pharm. Bull. 2006; 29(1):135-40. https://doi.org/10.1248/bpb.29.135
- Nosach LN, Povnitsa OYu, Rudneva II, Shauda VG. [Application of water extracts from cysts of Artemia as an antiviral agent with anti-adenoviral and anti-herpetic activity] Ukraine Patent 87251. June 25, 2009. Russian.
- Rushikesh S, Pravin P, Seetharama J. Peptides, Peptidomimetics, and polypeptides from marine sources: A wealth of natural sources for pharmaceutical applications. Mar. Drugs. 2017; 15:124-61. https://doi.org/10.3390/md15040124
- Strand M, Carlsson M, Uvell H, Islam K, Edlund K, Cullman I, et al. Isolation and characterization of anti-adenoviral secondary metabolites from marine actinobacteria. Mar. Drugs. 2014; 12(2):799-821. https://doi.org/10.3390/md12020799
- da Mata EC., Mourao CB, Rangel M, Schwartz EF. Antiviral activity of animal venom peptides and related compounds. Journal of Venomous Animals and Toxins including Tropical Diseases. 2017; 23:3-15. https://doi.org/10.1186/s40409-016-0089-0
- Palchikovskaya LG, Vasilchenko OV. Platonov MO, Starosyla D B, Porva JI, Rymar S J, et al. [Antiviral properties of plant flavonoids inhibitors of DNA and RNA synthesis]. Biopolymers and cell. 2013; 29(2):150-6. Ukrainian. https://doi.org/10.7124/bc.000813
- Pechenka AM, Grinevich AI, Kryuchko TA, Shaginyan VR, Solomakha LN [Proteflasid: specific activity against hepatitis C virus in preclinical studies; efficiency and safety in the treatment of hepatitis B and C in clinical practice (systematic review)]. Clinical Infectiology and Parasitology. 2015; 2(13):80-99. Russian.
- Kurbanov DD, Musabayev EI, Aripdzhovan DS. [Proteplaside is new in the treatment of viral infections (HPV, HSV, CMV) in obstetrics, gynecology and perinatology. Methodical recommendations]. Tashkent: 2007. Russian.
- Kaminsky V, Chernyshov V, Grynevych O, Benyuk V, Kornatskaya A, Shalko M, et al. Proteflazid and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital Infections. Pol Med J. 2017; 42(249):110-15.
- Kodama E, Shigeta S, Suzuki T, De Clerq E. Application of gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method. Antiviral Research. 1996; 31:159-64. https://doi.org/10.1016/0166-3542(96)06966-5
- Nosach LN, Povnitsa OYu. [Preclinical study of specific antiviral action of drugs in cell culture on the adenovirus model. Methodical recommendations]. Bulletin of Pharmacology and Pharmacy. 2007; 9:52-64. Russian.
- Shcherbinskaya AM, Dyachenko NS, Rybalko SL, Nosach LN, Dyadyun ST, Vrinchanu NA. [Antiviral Study of Potential Medicines. In: Stefanov A.V. eds. Preclinical studies of drugs. Methodical recommendations]. Kyiv: Avicenna; 2002:394-420. Russian.
- Dzyublyk IV, Dyachenko NS, Rybalko SL, Shcherbinskaya AM, Nosach LM, Voronenko SG, Poroghnitsky VG. [Manual on chemotherapy of viral infections. Educational and methodical manual for doctors]. Kyiv Medical Academy of Postgraduate Education of the Ministry of Health of Ukraine Kyiv: 2004. Ukrainian.
- Zavelevich M, Dyadyun S, Ribalko S. [Interferonogenie and apoptosis-modulating activity of the drug protelazid]. Visnik Vinnickogo derzhavnogo Universitetu. 2002; 6(2):281-3. Russian.