scholarly journals Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3678
Author(s):  
Olga V. Andreeva ◽  
Bulat F. Garifullin ◽  
Vladimir V. Zarubaev ◽  
Alexander V. Slita ◽  
Iana L. Yesaulkova ◽  
...  

A series of 1,2,3-triazolyl nucleoside analogues in which 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via polymethylene linkers to both nitrogen atoms of the heterocycle moiety (uracil, 6-methyluracil, thymine, quinazoline-2,4-dione, alloxazine) or to the C-5 and N-3 atoms of the 6-methyluracil moiety was synthesized. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. Antiviral assays revealed three compounds, 2i, 5i, 11c, which showed moderate activity against influenza virus A H1N1 with IC50 values of 57.5 µM, 24.3 µM, and 29.2 µM, respectively. In the first two nucleoside analogues, 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via butylene linkers to N-1 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine, respectively). In nucleoside analogue 11c, two 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached via propylene linkers to the C-5 and N-3 atoms of the 6-methyluracil moiety. Almost all synthesized 1,2,3-triazolyl nucleoside analogues showed no antiviral activity against the coxsackie B3 virus. Two exceptions are 1,2,3-triazolyl nucleoside analogs 2f and 5f, in which 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached to the C-5 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine respectively). These compounds exhibited high antiviral potency against the coxsackie B3 virus with IC50 values of 12.4 and 11.3 µM, respectively, although both were inactive against influenza virus A H1N1. According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 2i, 5i, and 11c against the H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRp). As to the antiviral activity of nucleoside analogs 2f and 5f against coxsackievirus B3, it can be explained by their interaction with the coat proteins VP1 and VP2.

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Dalya Al-Saad ◽  
Misal Giuseppe Memeo ◽  
Paolo Quadrelli

Influenza virus flu A H1N1 still remains a target for its inhibition with small molecules. Fleeting nitrosocarbonyl intermediates are at work in a short-cut synthesis of carbocyclic nucleoside analogues. The strategy of the synthetic approaches is presented along with thein vitroantiviral tests. The nucleoside derivatives were tested for their inhibitory activity against a variety of viruses. Promising antiviral activities were found for specific compounds in the case of flu A H1N1.


2012 ◽  
Vol 12 ◽  
pp. 290-295
Author(s):  
M Rajbhandari ◽  
Th Schoepke

In the course of screening of plant extracts for anti-influenza viral activity, 50% aqueous methanolic extract exhibited antiviral activity against influenza virus A. Bio-assay guided fractionation of the extract led to the indication of the presence of condensed tannins as the active constituents. This was confirmed by chemical tests as well as by thin layer chromatographic comparison with known tannin containing plant extracts. The active fractions were also analysed for the presence of carbohydrates by gas chromatography.DOI: http://dx.doi.org/10.3126/njst.v12i0.6515 Nepal Journal of Science and Technology 12 (2011) 290-295


2015 ◽  
Vol 10 (9) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Elza Karimova ◽  
Lidia Baltina ◽  
Leonid Spirikhin ◽  
Tagir Gabbasov ◽  
Yana Orshanskaya ◽  
...  

Reaction of quercetin (QR) (1) with bromine under various conditions was studied. Interaction of QR with 2–3 equiv. of bromine in glacial acetic acid at 35–40°C for 2–4 h and 20–22°C for 24 h led to the formation of QR 6,8-dibromide (2) (52–54% yields, 96–98% purity by HPLC). Interaction of QR with 2–5 equiv. bromine in absolute ethanol at 0–5°C and 20–22°C for 24 h led to the formation of 3- O-ethyl-QR-2,3,6,8,5′-pentabromide (3) (95–97% purity by HPLC) the output of which depends on the quantity of bromine. It was shown in MDCK cell culture that compound 2 exhibits a moderate inhibitory activity against pandemic influenza virus A/H1N1/pdm09 (EC50 6.0 μg/mL, CTD50 97.7 μg/mL, SI 16). Compound 3 was inactive.


Author(s):  
А.Г. Емельянова ◽  
М.В. Никифорова ◽  
Е.С. Дон ◽  
Н.Р. Махмудова ◽  
И.Н. Фалынскова ◽  
...  

Цель исследования - изучение возможного прямого влияния препарата «Анаферон детский» на жизненный цикл вируса гриппа А в процессе развития инфекции, а также дозозависимости противовирусного эффекта in vitro . Методика. Исследование противовирусной активности препарата «Анаферон детский» in vitro было проведено с использованием культуры клеток MDCK (Madin Darby canine kidney) и эталонных штаммов вируса гриппа A (H1N1) pdm09: A/California/07/09 и А/California/04/09, полученных от ВОЗ. Использовались методы оценки подавления Анафероном детским вирусной репликации (по результатам иммуноферментного анализа по определению экспрессии внутренних белков NP и M1 вируса гриппа А) и его влияние на ультраструктурные особенности морфогенеза вируса гриппа методом электронной микроскопии. В качестве положительного контроля был использован Озельтамивир карбоксилат в концентрации 10 мкМ. Для мониторинга валидности экспериментальной модели в работе использовали клетки, зараженные вирусом без добавления экспериментальных образцов (контроль вируса), а также интактные клетки (клеточный контроль). Результаты. В ходе исследования показан дозозависимый противовирусный эффект препарата «Анаферон детский» для 3 тестируемых разведений - 1/8, 1/12, 1/16. Методом электронной микроскопии показано, что применение препарата «Анаферон детский» при сравнении с контрольным образцом влияло на процесс почкования вирионов. Заключение. Впервые показана дозозависимость противовирусного действия препарата «Анаферон детский», а также подтверждена его эффективность в отношении двух штаммов вируса пандемического гриппа А/H1N1. Документировано, что применение препарата «Анаферон детский» нарушает жизненный цикл вируса гриппа А. Механизмы развития такого эффекта требуют дополнительного изучения, однако можно предположить их связь с ИФН-индуцирующими свойствами препарата «Анаферон детский», так как было показано, что в начале лечения вирусной инфекции препарат вызывает индукцию синтеза белков системы интерферонов. The aim of this study was to evaluate a possible direct effect of Anaferon for Children on the life cycle of influenza A virus during infection development and a dose response of the antiviral effect in vitro. Methods. The in vitro antiviral activity of Anaferon for Children was studied on cultured MDCK cells and reference strains of influenza virus A (H1N1) pdm09: A/California/07/09 and A/California/04/09, both from the WHO. Inhibition of viral replication by Anaferon for Children and its effect on ultrastructural features of the influenza morphogenesis were evaluated using electron microscopy. Results. The study demonstrated a dose dependence of Anaferon for Children antiviral activity for three dilutions - 1/8, 1/12, and 1/16. Anaferon for Children affected the process of virion budding as compared to placebo. Conclusion. The study showed that the anti-influenza action of Anaferon for Children was dose-dependent and confirmed that this drug was effective against two strains of pandemic A/H1N1 influenza. Furthermore, Anaferon for children disrupted one or several stages of the virus life cycle.


2013 ◽  
Vol 10 (6) ◽  
pp. 477-485 ◽  
Author(s):  
George V. Teplov ◽  
Evgeny V. Suslov ◽  
Vladimir V. Zarubaev ◽  
Anna A. Shtro ◽  
Liubov A. Karpinskaya ◽  
...  

2009 ◽  
Vol 6 (4) ◽  
pp. 517-522 ◽  
Author(s):  
M. Rajbhandari ◽  
R. Mentel ◽  
P. K. Jha ◽  
R. P. Chaudhary ◽  
S. Bhattarai ◽  
...  

Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated forin vitroantiviral activity against Herpes simplex virus type 1 (HSV-1) and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts ofAstilbe rivularis, Bergenia ciliata, Cassiope fastigiataandThymus linearisshowed potent anti-herpes viral activity. The extracts ofAllium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliataandVerbascum thapsusexhibited strong anti-influenza viral activity. Only the extracts ofA. rivularisandB. ciliatademonstrated remarkable activity against both viruses.


2010 ◽  
Vol 149 (5) ◽  
pp. 612-614 ◽  
Author(s):  
L. N. Shishkina ◽  
M. O. Skarnovich ◽  
A. S. Kabanov ◽  
A. A. Sergeev ◽  
S. E. Olkin ◽  
...  

Author(s):  
Thongchai Taechowisan ◽  
Tipparat Samsawat ◽  
Chanjira Jaramornburapong ◽  
Weerachai Phutdhawong ◽  
Waya S. Phutdhawong

Aims: The purpose of this study was to synthesis novel amine-geldanamycin hybrids (AGH) and evaluate their biological properties. Study Design: Experimental study. Place and Duration of Study: The study was carried out at the Department of Microbiology and Department of Chemistry, Faculty of Science, Silpakorn University, from December 2019 - November 2020. Methodology: Three new amine-geldanamycin hybrids (AGH); compounds 2 to 4 were synthesised by nucleophilic substitution of geldanamycin (1). The solubility, cytotoxicity, antiviral activity and molecular docking analyses were carried out. Results: The solubility of AGH in water was 1.918-5.571 mM, higher than that of compound 1. Compound 2 exhibited weak cytotoxicity activity against Vero and LLC-MK2 cells, with IC50 values of 229.19 and 330.58 µg/ml, respectively. All compounds inhibited influenza virus propagation in embryonated chicken eggs at the lowest amount of 1.25 µg per egg. They interacted positively with Hsp90, showing a binding free energy (DG) of -112.00 to -116.34 kcal/mol, which indicated lower Hsp90 affinity compared with that of geldanamycin (-133.06 kcal/mol) and 17-dimethylamino ethylamino-17-demethoxygeldanamycin (-136.55 kcal/mol), despite being bound in the similar active site. For the viral absorption, only AGH inhibited hemagglutination at a concentration of 25 µg/ml. Conclusion: The study findings revealed, through molecular docking analysis, that the development of AGH improved the antiviral activity. The AGH inhibited not only influenza virus propagation, but also viral absorption. Therefore, AGH could be considered a new choice for antiviral agents.


2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Lubomira Nikolaeva-Glomb ◽  
Luchia Mukova ◽  
Nadya Nikolova ◽  
Ilian Badjakov ◽  
Ivayla Dincheva ◽  
...  

Wild berry species are known to exhibit a wide range of pharmacological activities. They have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. The aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in Bulgaria: strawberry ( Fragaria vesca L.) and raspberry ( Rubus idaeus L.) of the Rosaceae plant family, and bilberry ( Vaccinium myrtillis L.) and lingonberry ( Vaccinium vitis-idaea L) of the Ericaceae. The antiviral effect has been tested against viruses that are important human pathogens and for which chemotherapy and/or chemoprophylaxis is indicated, namely poliovirus type 1 (PV-1) and coxsackievirus B1 (CV-B1) from the Picornaviridae virus family, human respiratory syncytial virus A2 (HRSV-A2) from the Paramyxoviridae and influenza virus A/H3N2 of Orthomyxoviridae. Wild berry fruits are freeze-dried and ground, then total methanol extracts are prepared. Further the extracts are fractioned by solid phase extraction and the non-anthocyanin and anthocyanin fractions are eluted. The in vitro antiviral effect is examined by the virus cytopathic effect (CPE) inhibition test. The results reveal that the total extracts of all tested berry fruits inhibit the replication of CV-B1 and influenza A virus. CV-B1 is inhibited to the highest degree by both bilberry and strawberry, as well as by lingonberry total extracts, and influenza A by bilberry and strawberry extracts. Anthocyanin fractions of all wild berries strongly inhibit the replication of influenza virus A/H3N2. Given the obtained results it is concluded that wild berry species are a valuable resource of antiviral substances and the present study should serve as a basis for further detailed research on the matter.


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