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Nikolova I.,Bulgarian Academy of Science | Galabov A.S.,Bulgarian Academy of Science | Petkova R.,Scientific Technological Service Ltd | Chakarov S.,Sofia University | Atanasov B.,Bulgarian Academy of Science
Zeitschrift fur Naturforschung - Section C Journal of Biosciences

Disoxaril inhibits enterovirus replication by binding to the hydrophobic pocket within the VP1 coat protein, thus stabilizing the virion and blocking its uncoating. Disoxaril-resistant (RES) mutants of the Coxsackie virus B1 (CVB1/RES) were derived from the wild disoxaril- sensitive (SOF) strain (CVB1/SOF) using a selection approach. A disoxaril-dependent (DEP) mutant (CVB1/DEP) was obtained following nine consecutive passages of the disoxaril- resistant mutant in the presence of disoxaril. Phenotypic characteristics of the disoxaril mutants were investigated. A timing-of-addition study of the CVB1/DEP replication demonstrated that in the absence of disoxaril the virus particle assembly stopped. VP1 RNA sequences of disoxaril mutants were compared with the existing Gen Bank CVB1 reference structure. The amino acid sequence of a large VP1 196 - 258 peptide (disoxaril-binding region) of CVB1/RES was significantly different from that of the CVB1/SOF. Crucially important changes in CVB1/RES were two point mutations, M213H and F237L, both in the ligand-binding pocket. The sequence analysis of the CVB1/DEP showed some reversion to CVB1/SOF. The amino acid sequences of the three VP1 proteins are presented. © 2011 Verlag der Zeitschrift für Naturforschung, Tübingen. Source

Arabadjiev B.,Sofia University | Arabadjiev B.,Scientific Technological Service Ltd | Petkova R.,Scientific Technological Service Ltd | Chakarov S.,Sofia University | And 3 more authors.
Biotechnology and Biotechnological Equipment

The enormous potential of human embryonic stem cells is fueling continuous research aimed at establishment of new lines of these cells. Currently, research groups from 24 countries have reported derivation of over 1000 human embryonic stem cell lines. Because of the controversy surrounding the derivation of these cells from human embryos it is important to clarify whether the existing hESC lines are sufficient for basic research and future therapeutic applications. Here we briefly review some of the most important arguments justifying the need for continuing derivation of human embryonic stem cell lines. Source

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