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From the traditional Chinese medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors
Lijia Xu , Nicole Grandi , Claudia Del Vecchio , Daniela Mandas , Angela Corona , Dario Piano , Francesca Esposito , Cristina Parolin , Enzo Tramontano
J. Microbiol. 2015;53(4):288-293.   Published online March 4, 2015
DOI: https://doi.org/10.1007/s12275-015-4652-0
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AbstractAbstract
HIV-1 reverse transcriptase (RT) is still an extremely attractive pharmaceutical target for the identification of new inhibitors possibly active on drug resistant strains. Medicinal plants are a rich source of chemical diversity and can be used to identify novel scaffolds to be further developed by chemical modifications. We investigated the ability of the main lignans from Schisandra chinensis (Turcz.) Baill. fruits, commonly used in Traditional Chinese Medicine, to affect HIV-1 RT functions. We purified 6 lignans from Schisandra chinensis fruits and assayed their effects on HIV-1 RT and viral replication. Among the S. chinensis fruit lignans, Schisandrin B and Deoxyschizandrin selectively inhibited the HIV-1 RTassociated DNA polymerase activity. Structure activity relationship revealed the importance of cyclooctadiene ring substituents for efficacy. In addition, Schisandrin B was also able to impair HIV-1 RT drug resistant mutants and the early phases of viral replication. We identified Schisandrin B and Deoxyschizandrin as new scaffold for the further development of novel HIV-1 RT inhibitors.

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A Novel Retron of Vibrio parahaemolyticus Is Closely Related to Retron-Vc95 of Vibrio cholerae
Toshi Shimamoto , Ashraf M. Ahmed , Tadashi Shimamoto
J. Microbiol. 2013;51(3):323-328.   Published online June 28, 2013
DOI: https://doi.org/10.1007/s12275-013-2715-7
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AbstractAbstract
Some bacteria produce a satellite RNA-DNA complex termed msDNA, multicopy single-stranded DNA. In this report, msDNA from Vibrio parahaemolyticus, a cause of acute gastroenteritis, was identified and named msDNA-Vp96. The retron element containing the ret gene, encoding the reverse transcriptase (RT) that is responsible for msDNA production, was cloned and characterized. Comparison of msDNAVp96 and msDNA-Vc95, from Vibrio cholerae, showed a high level of sequence similarity. We exchanged the two ret genes to examine whether msDNA was produced by the RT from different sources. We found that RT-Vp96 of V. parahaemolyticus was able to synthesize msDNA-Vc95 of V. cholerae and vice versa. To the best of our knowledge, this is the first report that RT from different bacterial species can synthesize msDNA.
A Proteomic Approach to Study msDNA Function in Escherichia coli
Mi-Ae Jeong , Dongbin Lim
J. Microbiol. 2004;42(3):200-204.
DOI: https://doi.org/2089 [pii]
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AbstractAbstract
Retron is a prokaryotic genetic element that produces multicopy single-stranded DNA covalently linked to RNA (msDNA) by a reverse transcriptase. It was found that cells producing a large amount of msDNA, rather than those that did not, showed a higher rate of mutation. In order to understand the molecular mechanism connecting msDNA production to the high mutation rate the protein patterns were compared by two dimensional gel electrophoresis. Ten proteins were found to be differentially expressed at levels more than three fold greater in cells with than without msDNA, nine of which were identified by MALDI TOF MS. Eight of the nine identified proteins were repressed in msDNA-producing cells and, surprisingly, most were proteins functioning in the dissimilation of various carbon sources. One protein was induced four fold greater in the msDNA producing cells and was identified as a 30S ribosomal protein S2 involved in the regulation of translation. The molecular mechanism underlying the elevated mutation in msDNA-producing cell still remains elusive.

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