rologie i - European Congress of Virology

5 th European Congress of Virology31 were selected for the design and synthesis of analogues, with the aimof increasing the potency of the compounds. Some of the analogues werenon cytotoxic in a panel of cell lines and more potent than the originalcompounds, exhibiting a strong inhibition of the physical interactionbetween the PA and PB1 subunits of influenza virus RNA polymerasecomplex, both in vitro and in cells. Moreover, the most promising analogueswere able to inhibit the replication of a panel of influenza A and Bvirus strains, including an oseltamivir resistant isolate, at low micromolarconcentrations. In addition, these compounds did not inhibit the replicationof other RNA or DNA viruses, demonstrating to possess specific antiviralactivity against influenza viruses. Taken together, our results suggest thatthese compounds could provide the basis for the development of a newgeneration of therapeutic agents against influenza A and B viruses.REF 118Changes of fermental system in organism of white mice at ExperimentalFlu under the influence of Piler lightTatyana SOVA 1 , Oksana LAGODA 1 , Valentina DIVOCHA 1Ukrainian Research Institute for Medicine of Transport, Odessa,UKRAINENormal functioning of both a human and an animal depends on variousvital power sources: light, air, waters, food and electromagnetic wavesarriving from the environment.Objective: to study the PILER (Polarized, Incoherent, Low Energy Radiation)light action on proteinase, infectious, hemagglutinating activity in anorganism of white mice at experimental flu.Materials and methods: 40 white mice (the line Balb/c, weight 13 14 gr),A/PR/8/34(H1N1) the flu virus, the device with PILER light. Infection ofmice with the flu virus has been carried out intranasal under anesthesia.The animals have been randomized into 4 groups, 10 animals in everygroup. The first group was the control one for the animals. The secondgroup of animals was exposed to the influence PILER – light (control).The third group of animals was infected with a lethal dose of the flu Avirus. The fourth group also caught a lethal dose of the flu A virus andwas exposed to the influence PILER light (treatment). Each mouse of thegroups under experiment received 11 sessions of PILER light influence.Results: proteinase, infectious, hemagglutinating activity and protein inthe lungs and blood serum of healthy mice did not differ much from thosein the group of healthy animals irradiated with PILER light. The treatmentof the animals previously infected with a lethal dose of virus A flu withPILER light detained the virus’s reproduction for a day. Infectious andhemagglutinating activity was lower in comparison with those in controlgroup for virus. 20% of animals, having been treated with PILER light,were alive by the 14th days after infection, while 100% fatality of animalsin the control group took place by the sixth days after infection.Conclusions: PILER light strengthens protective forces of an organism atflu.REF 119The crystal structure of the foot and mouth disease virus leader proteasein complex with E 64 R P NH2 provides new insights on itssubstrate specificityJutta STEINBERGER 1 , Irina GRISHKOVSKAYA 2 , Tim SKERN 11 Department of Medical Biochemistry, Max F. Perutz Laboratories, MedicalUniversity of Vienna, Vienna, AUSTRIA; 2 Department of Structuraland Computational Biology, Max F. Perutz Laboratories, University ofVienna, Vienna, AUSTRIAThe Leader protease (Lbpro) of the Foot and mouth disease virus is essentialfor the successful replication of the virus. Leaderless virus was shownto be attenuated and not able to spread within the infected host. Therefore,Lbpro represents a promising target for the development of antiviralcompounds. Though being one of the smallest members of papain likecysteine proteases, Lbpro shows great substrate specificity ranging fromP7 to P5 ′ . Moreover, Lbpro only accepts a positively charged residue ateither the P1 or the P1 ′ position; substrates containing basic residues atboth positions are inhibitory. Recent data on the specificity determinantsat the P’ side inspired the extension of E64, a well known epoxide basedinhibitor of cysteine proteases, by the dipeptides Gly Pro NH2 or Arg ProNH2. Both modified inhibitors, termed E 64 G P NH2 and E 64 R P NH2,could improve the Ki of E64 (3.4 M) to 1.3 M and 0.03 M, respectively.These findings suggest an important role for Arg at the P1 ′ position.However, the crystal structure of Lbpro in complex with the inhibitor E 64R P NH2 is lacking electron density for the side chain of the P1 ′ Arg fromthe Cgamma atom onwards, despite being in close proximity to D49 andE147. Consequently, we aim to investigate the importance of the residuesD49 and E147 for the interaction with Arg at position P1 ′ .Our findingsshould provide further knowledge to improve inhibitor design and maylead to the development of a more potent and specific inhibitor againstFMDV infections.REF 120Antiviral properties of edible berriesAizhan TURMAGAMBETOVA, Nadezhda SOKOLOVA, IrinaZAITCEVA, Andrey BOGOYAVLENSKIY, Vladimir BEREZINInstitute of microbiology and virology, Almaty, KAZAKHSTANVariety therapeutic properties of plants are caused by the presence of alarge in their composition and structure chemicals (alkaloids, glycosides,saponins, vitamins, tannins, essential oils, etc.), which have a pharmacologicaleffect on the human organism, and the cause of the disease.Therefore the study of the possibility of using of herbal remedies forthe treatment of viral infections is the actual problem of Pharmacognosyand virology. The aim of research was to study the antiviral effect ofextracts obtained from elderberry, lingonberry, barberry, bird cherry and2 grapes (“Isabella” and “Muscat”) on the activity of the influenza virusstrain A/Alma Ata/8/98 (H3N2). Choice of plants was due to the presenceof polyphenolic compounds belonging to the different chemical nature.The antiviral activity of the research berries in the dose range of 1 to100 mg/kg body weight was studied for their ability to inhibit the reproductionof 100 infectious doses of influenza virus. It is shown that in dose of100 mg per kg extracts derives from berries of elderberry, barberry, lingonberryand bird cherry exhibit high virus inhibitory and virucidal properties,enabling their use as additional antiviral therapy. Extracts obtained fromdifferent grape varieties, in the tested range of doses did not show antiviralactivity.REF 121Virucidal activity of Morus spp. plant extracts on Caliciviridae: theimpact on a human norovirus surrogateMihayl VARBANOV 1,2 , Ines THABTI 1,2,3 , Thomas KASSAB 1,2 , AliAFERCHICHI 3 , Raphael E. DUVAL 1,21 CNRS, UMR 7565, SRSMC, Nancy, FRANCE; 2 Université de Lorraine,Faculté de Pharmacie, Nancy, FRANCE; 3 Laboratoire d’Aridoculture etCultures Oasiennes, Medenine, TUNISIAHuman noroviruses (HNoV) are highly pathogenic viruses belonging tothe Caliciviridae family, responsible for worldwide epidemic outbreaksof gastroenteritis, and thus representing a heavy burden to infants andimmunologically disadvantaged hosts. To date, there is still no specifictreatment for HNoV. In this aspect, natural products offer an alternativein terms of innovative drug therapies. The object of this study was todetermine the antiviral properties of leaves and stem bark of the mulberryVirologie, Vol 17, supplément 2, septembre 2013S151