Inhibition of Cysteine Proteases via Thiol-Michael Addition Explains the Anti-SARS-CoV-2 and Bioactive Properties of Arteannuin B Kaitlyn Varela, Hadi D. Arman, Mitchel S. Berger, Valerie M. Sponsel, Chin-Hsing Annie Lin, Francis K. Yoshimoto Journal of Natural Products, 2023 Artemisia annua is the plant that produces artemisinin, an endoperoxide-containing sesquiterpenoid used for the treatment of malaria. A. annua extracts, which contain other bioactive compounds, have been used to treat other diseases, including cancer and COVID-19, the disease caused by the virus SARS-CoV-2. In this study, a methyl ester derivative of arteannuin B was isolated when A. annua leaves were extracted with a 1:1 mixture of methanol and dichloromethane. This methyl ester was thought to be formed from the reaction between arteannuin B and the extracting solvent, which was supported by the fact that arteannuin B underwent 1,2-addition when it was dissolved in deuteromethanol. In contrast, in the presence of N-acetylcysteine methyl ester, a 1,4-addition (thiol-Michael reaction) occurred. Arteannuin B hindered the activity of the SARS CoV-2 main protease (nonstructural protein 5, NSP5), a cysteine protease, through time-dependent inhibition. The active site cysteine residue of NSP5 (cysteine-145) formed a covalent bond with arteannuin B as determined by mass spectrometry. In order to determine whether cysteine adduction by arteannuin B can inhibit the development of cancer cells, similar experiments were performed with caspase-8, the cysteine protease enzyme overexpressed in glioblastoma. Time-dependent inhibition and cysteine adduction assays suggested arteannuin B inhibits caspase-8 and adducts to the active site cysteine residue (cysteine-360), respectively. Overall, these results enhance our understanding of how A. annua possesses antiviral and cytotoxic activities.
Signal Achievements in Gibberellin Research: The Second Half-Century Valerie M. Sponsel Annual Plant Reviews the Gibberellins, 2016 Chapter 1 briefly recounts the discovery of gibberellins (GAs) as natural products of the fungus Gibberella fujikuroi in the early part of the twentieth century, and provides a historical overview of GA research from the late 1950s to the present day. It describes howbiosynthetic pathways toGAs inGibberella and higher plants were defined, and how stem length mutants of cereals and legumes were instrumental in establishing which GAs are biologically active and have hormonal function. The chapter presents an overview of the cereal aleurone system in which GA signalling was first studied, and describes how more recent use of Arabidopsis and rice led to the characterisation of a GA receptor (GID1) and downstream regulatory proteins (DELLAs). A number of DELLA-interacting proteins are described, illustrating how it is that GA-induced degradation of DELLAs facilitates downstream responses including cell elongation. Other ‘classical’ GA responses include germination and flowering in some species.
A Century of Gibberellin Research Peter Hedden, Valerie Sponsel Journal of Plant Growth Regulation, 2015 Gibberellin research has its origins in Japan in the 19th century, when a disease of rice was shown to be due to a fungal infection. The symptoms of the disease including overgrowth of the seedling and sterility were later shown to be due to secretions of the fungus Gibberella fujikuroi (now reclassified as Fusarium fujikuroi), from which the name gibberellin was derived for the active component. The profound effect of gibberellins on plant growth and development, particularly growth recovery in dwarf mutants and induction of bolting and flowering in some rosette species, prompted speculation that these fungal metabolites were endogenous plant growth regulators and this was confirmed by chemical characterisation in the late 1950s. Gibberellins are now known to be present in vascular plants, and some fungal and bacterial species. The biosynthesis of gibberellins in plants and the fungus has been largely resolved in terms of the pathways, enzymes, genes and their regulation. The proposal that gibberellins act in plants by removing growth limitation was confirmed by the demonstration that they induce the degradation of the growth-inhibiting DELLA proteins. The mechanism by which this is achieved was clarified by the identification of the gibberellin receptor from rice in 2005. Current research on gibberellin action is focussed particularly on the function of DELLA proteins as regulators of gene expression. This review traces the history of gibberellin research with emphasis on the early discoveries that enabled the more recent advances in this field.
Soil-strength enhancements from polymer-infused roots Miguelangel Sauceda, Drew W. Johnson, Jie Huang, Sazzad Bin-Shafique, Valerie M. Sponsel, Mark Appleford Journal of Geotechnical and Geoenvironmental Engineering, 2014 This research investigates the use of polymer-infused roots for soil-improvement applications. By infusing polymer through the easily accessible above-surface plant stems, polymer-infused roots can be created without subsurface excavations. Evaluation of this technique involves identifying the improvements from polymer-infused roots by measuring in situ shear strength of soil using a vane shear apparatus and by measuring the tensile strength using split-tension tests in the laboratory. Roots of Ruellia squarrosa and Artemisia annua plants were infused with a mixture of epoxy resin and polyoxyalkylamine blend hardener. Compared with noninfused roots, polymer-infused roots provided an additional 22 kPa (28%) of shear strength for elastic silt and an additional 13.1 kPa (25%) of shear strength for low-plasticity clay with a corresponding 13.6-kPa (55%) increase in tensile strength for the low-plasticity clay. Acid hydrolysis testing was performed to ascertain the potential durability of the polymer-i...
Durability of polymer infused roots used for soil stabilization Miguelangel Sauceda, Drew W. Johnson, Jie Huang, Sazzad Bin-Shafique, Valerie M. Sponsel, Mark Appleford Journal of Materials in Civil Engineering, 2014 Polymer-infused plant roots can be created without soil excavation by infusing polymer into the roots of plants through the easily accessible above-surface plant stems. Efficacy of this technique for use in soil stabilization applications involves assessing the durability of polymer-infused plant roots. Polymer content was determined for infused Artemisia annua plant roots. Durability of these polymer-infused roots was evaluated by mass loss resistance and strength loss resistance of acid-treated samples. Durability in the context of soil stabilization applications was determined by comparing the shear strength of aged samples. Polymer infusions improved the durability of the plant material. Infused plant stems incubated in acid for 15 weeks lost 29% mass, whereas noninfused stems lost 60% mass. Infused roots incubated in acid for 24 h retained a tensile strength of 25 MPa, whereas noninfused acid-treated roots had a tensile strength of 12 MPa. In comparison to plant roots that provided no enhance...
Strength enhancement of plant roots through polymer infusions Karl W Eisenacher, Drew W Johnson, Mark Appleford, Valerie M Sponsel Journal of Composite Materials, 2013 By infusing a thermoset epoxy polymer into the root system of a plant, we aim to create an in situ plant-polymer composite material of high tensile strength resistant to biodegradation and suitable for soil stabilization applications. Microscopy imaging, volume and mass measurements, thermogravimetric analysis, and tensile testing were conducted to characterize the effects of infusing polymer into the plant system. The polymer appears to travel predominantly through xylem vessels of the plant system during infusions. Maximum tensile strength and modulus of elasticity are increased by 107% and 92%, respectively, with a polymer content of 59% by mass after infusions were conducted.
Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana. Jianhua Ruan, Joseph Perez, Brian Hernandez, Chengwei Lei, Garry Sunter, Valerie M Sponsel BMC Bioinformatics, 2011 BACKGROUND: Several large-scale gene co-expression networks have been constructed successfully for predicting gene functional modules and cis-regulatory elements in Arabidopsis (Arabidopsis thaliana). However, these networks are usually constructed and analyzed in an ad hoc manner. In this study, we propose a completely parameter-free and systematic method for constructing gene co-expression networks and predicting functional modules as well as cis-regulatory elements. RESULTS: Our novel method consists of an automated network construction algorithm, a parameter-free procedure to predict functional modules, and a strategy for finding known cis-regulatory elements that is suitable for consensus scanning without prior knowledge of the allowed extent of degeneracy of the motif. We apply the method to study a large collection of gene expression microarray data in Arabidopsis. We estimate that our co-expression network has ~94% of accuracy, and has topological properties similar to other biological networks, such as being scale-free and having a high clustering coefficient. Remarkably, among the ~300 predicted modules whose sizes are at least 20, 88% have at least one significantly enriched functions, including a few extremely significant ones (ribosome, p < 1E-300, photosynthetic membrane, p < 1.3E-137, proteasome complex, p < 5.9E-126). In addition, we are able to predict cis-regulatory elements for 66.7% of the modules, and the association between the enriched cis-regulatory elements and the enriched functional terms can often be confirmed by the literature. Overall, our results are much more significant than those reported by several previous studies on similar data sets. Finally, we utilize the co-expression network to dissect the promoters of 19 Arabidopsis genes involved in the metabolism and signaling of the important plant hormone gibberellin, and achieved promising results that reveal interesting insight into the biosynthesis and signaling of gibberellin. CONCLUSIONS: The results show that our method is highly effective in finding functional modules from real microarray data. Our application on Arabidopsis leads to the discovery of the largest number of annotated Arabidopsis functional modules in the literature. Given the high statistical significance of functional enrichment and the agreement between cis-regulatory and functional annotations, we believe our Arabidopsis gene modules can be used to predict the functions of unknown genes in Arabidopsis, and to understand the regulatory mechanisms of many genes.
Systematic construction and analysis of co-expression networks for identification of functional modules and cis-regulatory elements Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, 2010
Signal achievements in gibberellin research: the second half‐century VM Sponsel Annual Plant Reviews, Volume 49: Gibberellins, The, 1-36 , 2016 2016 Citations: 41
Plant root templated irrigation M Qasemi, DW Johnson, VM Sponsel Irrigation and Drainage 65 (1), 38-48 , 2016 2016 Citations: 2
A century of gibberellin research P Hedden, V Sponsel Journal of plant growth regulation 34 (4), 740-760 , 2015 2015 Citations: 790
Durability of polymer infused roots used for soil stabilization M Sauceda, DW Johnson, J Huang, S Bin-Shafique, VM Sponsel, ... Journal of materials in civil engineering 26 (8), 04014043 , 2014 2014 Citations: 2
Soil-strength enhancements from polymer-infused roots M Sauceda, DW Johnson, J Huang, S Bin-Shafique, VM Sponsel, ... Journal of Geotechnical and Geoenvironmental Engineering 140 (2), 04013004 , 2014 2014 Citations: 26
B2. The Biosynthesis and Metabolism of VM Sponsel Plant Hormones: Physiology, Biochemistry and Molecular Biology 93, 66 , 2013 2013
TREVOR L. WANG VM SPONSEL The Pea Crop: A Basis for Improvement, 339 , 2013 2013
Strength enhancement of plant roots through polymer infusions KW Eisenacher, DW Johnson, M Appleford, VM Sponsel Journal of composite materials 47 (11), 1313-1326 , 2013 2013 Citations: 6
Systematic identification of functional modules and cis-regulatory elements in Arabidopsis thaliana J Ruan, J Perez, B Hernandez, C Lei, G Sunter, VM Sponsel BMC bioinformatics 12 (Suppl 12), S2 , 2011 2011 Citations: 15
Travel Funds for Junior Scientists to attend the International Plant Growth Substances Association Conference VM Sponsel NSF Award Number 1038329. Directorate for Biological Sciences 10 (1038329 … , 2010 2010
Systematic construction and analysis of co-expression networks for identification of functional modules and cis-regulatory elements J Ruan, J Perez, B Hernandez, G Sunter, VM Sponsel Proceedings of the 9th International Workshop on Data Mining in … , 2010 2010 Citations: 2
Plant hormones VM Sponsel, P Hedden, PJ Davies Springer , 2010 2010 Citations: 18
A combined biochemical, molecular and computational approach to understanding the regulation of gibberellin biosynthesis in Arabidopsis VM Sponsel NSF Award Number 0848135. Directorate for Biological Sciences 8 (848135), 48135 , 2009 2009
The major antennal chemosensory protein of red imported fire ant workers D González, Q Zhao, C McMahan, D Velasquez, WE Haskins, V Sponsel, ... Insect Molecular Biology 18 (3), 395-404 , 2009 2009 Citations: 91
Strategies for the analysis of biologically active compounds by capillary electrophoresis and microchip-capillary electrophoresis CD Garcia, W Gorski, A Ayon, V Sponsel 2009
Expression of gibberellin 20-oxidase1 ( AtGA20ox1 ) in Arabidopsis seedlings with altered auxin status is regulated at multiple levels I Desgagné-Penix, VM Sponsel Journal of Experimental Botany 59 (8), 2057-2070 , 2008 2008 Citations: 56
IPGSA Conference-Travel funds for junior scientists to attend the International Plant Growth Substances Association Conference in Puerto Vallarta, Mexico on July 21-25, 2007. VM Sponsel NSF Award Number 0726565. Directorate for Biological Sciences 7 (726565), 26565 , 2007 2007
Effects of altered growth on the plant hormones auxin and gibberellin in Arabidopsis thaliana . I Desgagné-Penix, V Sponsel 2006
The auxin transport inhibitor response 3 ( tir3 ) allele of BIG and auxin transport inhibitors affect the gibberellin status of Arabidopsis I Desgagné‐Penix, S Eakanunkul, JP Coles, AL Phillips, P Hedden, ... The Plant Journal 41 (2), 231-242 , 2005 2005 Citations: 55
MOST CITED SCHOLAR PUBLICATIONS
A century of gibberellin research P Hedden, V Sponsel Journal of plant growth regulation 34 (4), 740-760 , 2015 2015 Citations: 790
Gibberellin biosynthesis and inactivation VM Sponsel, P Hedden Plant hormones: biosynthesis, signal transduction, action!, 63-94 , 2004 2004 Citations: 299
Gibberellin biosynthesis and metabolism VM Sponsel Plant hormones and their role in plant growth and development, 43-75 , 1987 1987 Citations: 150
Qualitative and quantitative analyses of gibberellins throughout seed maturation in Pisum sativum cv. Progress No. 9 VM Frydman, P Gaskin, J & MacMillan Planta 118 (2), 123-132 , 1974 1974 Citations: 136
The biosynthesis and metabolism of gibberellins in higher plants VM Sponsel Plant hormones: physiology, biochemistry and molecular biology, 66-97 , 1995 1995 Citations: 103
The major antennal chemosensory protein of red imported fire ant workers D González, Q Zhao, C McMahan, D Velasquez, WE Haskins, V Sponsel, ... Insect Molecular Biology 18 (3), 395-404 , 2009 2009 Citations: 91
The localization, metabolism and biological activity of gibberellins in maturing and germinating seeds of Pisum sativum cv. Progress No. 9 VM Sponsel Planta 159 (5), 454-468 , 1983 1983 Citations: 87
General aspects of phase change, with special reference to Hedera helix L. PF Wareing, VM Frydman Symposium on juvenility in woody perennials. Acta Hort 56, 57-69 , 1976 1976 Citations: 82
Metabolism of gibberellin A 29 in seeds of Pisum sativum cv. Progress No. 9; Use of [ 2 H] and [ 3 H]GAs, and the identification of a new GA catabolite VM Sponsel, J MacMillan Planta 144 (1), 69-78 , 1978 1978 Citations: 77
Gibberellins in developing fruits of Pisum sativum cv. Alaska: Studies on their role in pod growth and seed development JL García-Martínez, VM Sponsel, P Gaskin Planta 170 (1), 130-137 , 1987 1987 Citations: 75
Gibberellins in dark- and red-light-grown shoots of dwarf and tall cultivars of Pisum sativum : The quantification, metabolism and biological activity of gibberellins in … VM Sponsel Planta 168 (1), 119-129 , 1986 1986 Citations: 74
Endogenous gibberellins and kauranoids identified from developing and germinating barley grain P Gaskin, SJ Gilmour, JR Lenton, J MacMillan, VM Sponsel Journal of Plant Growth Regulation 2 (1), 229-242 , 1983 1983 Citations: 72
Further studies on the metabolism of gibberellins (GAs) A 9 , A 20 and A 29 in immature seeds of Pisum sativum cv. progress No. 9 VM Sponsel, J MacMillan Planta 135 (2), 129-136 , 1977 1977 Citations: 71
The metabolism of gibberellins A9, A20 and A29 in immature seeds of Pisum sativum cv. Progress No. 9 VM Frydman, J & MacMillan Planta 125 (2), 181-195 , 1975 1975 Citations: 71
Phase Change in Hedera helix L I. GIBBERELLIN-LIKE SUBSTANCES IN THE TWO GROWTH PHASES VM Frydman, PF Wareing J. Experimental Botany 24 (6), 1131-1138 , 1973 1973 Citations: 66
Identification and localization of gibberellins in maturing seeds of the cucurbit Sechium edule, and a comparison between this cucurbit and the legume Phaseolus coccineus KS Albone, P Gaskin, J MacMillan, VM Sponsel Planta 162 (6), 560-565 , 1984 1984 Citations: 65
Gibberellins in immature seeds and dark-grown shoots of Pisum sativum Gibberellins identified in the tall cultivar Alaska in comparison with those in the dwarf … P Gaskin, SJ Gilmour, J MacMillan, VM Sponsel Planta 163 (2), 283-289 , 1985 1985 Citations: 59
Expression of gibberellin 20-oxidase1 ( AtGA20ox1 ) in Arabidopsis seedlings with altered auxin status is regulated at multiple levels I Desgagné-Penix, VM Sponsel Journal of Experimental Botany 59 (8), 2057-2070 , 2008 2008 Citations: 56
Phase change in Hedera helix L. III. The effects of gibberellins, abscisic acid and growth retardants on juvenile and adult ivy VM Frydman, PF Wareing J. Experimental Botany 25, 420-429 , 1974 1974 Citations: 56
The auxin transport inhibitor response 3 ( tir3 ) allele of BIG and auxin transport inhibitors affect the gibberellin status of Arabidopsis I Desgagné‐Penix, S Eakanunkul, JP Coles, AL Phillips, P Hedden, ... The Plant Journal 41 (2), 231-242 , 2005 2005 Citations: 55