Libraries Spaces Series: Introduction

An introduction to the new multi-issue SOURCE series on Library spaces.

Vasyl Kapustyan (1942–2020) of blessed memory

The article represents the scientific achievements and work of a Ukrainian botanist, candidate of agricultural sciences, director of the O.V. Fomin Botanical Garden (1987–2006, 2008–2012), Vasyl Kapustyan, who died on August 19, 2020, after a long illness.Vasyl Kapustyan was born on July 24, 1942. In 1965 he graduated from the Ukrainian Agricultural Academy, and in 1972 received the degree of candidate of agricultural sciences. Since 1974, the work of Vasyl Kapustyan was associated with the O.V. Fomin Botanical Garden, where he served in 1975–1987 as deputy director and head of the sector of tropical and subtropical plants, in 1987–1997 – as director and head of the sector of tropical and subtropical plants, and from 1997 – exclusively as director of the Botanical Garden.The scientific work of Vasyl Kapustyan was related to the introduction of tropical and subtropical plants, their conservation, and rational use. He was the author of over 80 scientific articles and monographs, the last of which was dedicated to the 180th anniversary of the botanical garden. Since the founding of the series “Introduction and Conservation of Plant Diversity” of the “Bulletin of the Taras Shevchenko National University of Kyiv”, Vasyl Kapustyan was its editor-in-chief. He was also a member of the Academic Councils of Kyiv University and Faculty of Biology, chairman of the Academic Council of the Botanical Garden, a member of the Bureau of the Council of Botanical Gardens of Ukraine, and a member of the editorial board of the international scientific journal “Plant Introduction”. He was the founder and scientific director of the Museum of the Botanical Garden History, which opened in 2004.

Bicyclic azetidines kill the diarrheal pathogen Cryptosporidium in mice by inhibiting parasite phenylalanyl-tRNA synthetase

Cryptosporidium is a protozoan parasite and a leading cause of diarrheal disease and mortality in young children. Currently, there are no fully effective treatments available to cure infection with this diarrheal pathogen. In this study, we report a broad drug repositioning effort that led to the identification of bicyclic azetidines as a new anticryptosporidial series. Members of this series blocked growth in in vitro culture of three Cryptosporidium parvum isolates with EC50’s in 1% serum of <0.4 to 96 nM, had comparable potencies against Cryptosporidium hominis and C. parvum, and was effective in three of four highly susceptible immunosuppressed mice with once-daily dosing administered for 4 days beginning 2 weeks after infection. Comprehensive genetic, biochemical, and chemical studies demonstrated inhibition of C. parvum phenylalanyl-tRNA synthetase (CpPheRS) as the mode of action of this new lead series. Introduction of mutations directly into the C. parvum pheRS gene by CRISPR-Cas9 genome editing resulted in parasites showing high degrees of compound resistance. In vitro, bicyclic azetidines potently inhibited the aminoacylation activity of recombinant ChPheRS. Medicinal chemistry optimization led to the identification of an optimal pharmacokinetic/pharmacodynamic profile for this series. Collectively, these data demonstrate that bicyclic azetidines are a promising series for anticryptosporidial drug development and establish a broad framework to enable target-based drug discovery for this infectious disease.