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ACS Infect Dis 2021 Feb 16. Epub 2021 Feb 16.

Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, United Kingdom.

Protein and phosphoinositide kinases have been successfully exploited as drug targets in various disease areas, principally in oncology. In malaria, several protein kinases are under investigation as potential drug targets, and an inhibitor of phosphatidylinositol 4-kinase type III beta (PI4KIIIβ) is currently in phase 2 clinical studies. In this Perspective, we review the potential of kinases as drug targets for the treatment of malaria. Read More

Proc Natl Acad Sci U S A 2021 Jan;118(1)

Department of Plant Pathology, University of Kentucky, Lexington, KY 40546

Biogenesis of viral replication organelles (VROs) is critical for replication of positive-strand RNA viruses. In this work, we demonstrate that tomato bushy stunt virus (TBSV) and the closely related carnation Italian ringspot virus (CIRV) hijack the retromer to facilitate building VROs in the surrogate host yeast and in plants. Depletion of retromer proteins, which are needed for biogenesis of endosomal tubular transport carriers, strongly inhibits the peroxisome-associated TBSV and the mitochondria-associated CIRV replication in yeast and In vitro reconstitution revealed the need for the retromer for the full activity of the viral replicase. Read More

J Genet Genomics 2020 Oct 28;47(10):618-626. Epub 2020 Oct 28.

Experimental and Clinical Research Center (ECRC), A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Lindenberger Weg.80, Berlin, 13125, Germany. Electronic address:

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20-25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). Read More

ACS Infect Dis 2021 01 15;7(1):34-46. Epub 2020 Dec 15.

Department of Chemistry, University of Cape Town, Rondebosch, Cape Town 7701, South Africa.

Recent studies on 3,6-diphenylated imidazopyridazines have demonstrated impressive activity and efficacy in mouse models of malaria infection. Herein, we report the synthesis and antiplasmodium evaluation of a new series of amidated analogues and demonstrate that these compounds potently inhibit phosphatidylinositol-4-kinase (PI4K) type IIIβ while moderately inhibiting cyclic guanidine monophosphate (cGMP)-dependent protein kinase (PKG) activity . Using docking, we predict key binding interactions for these analogues within the adenosine triphosphate (ATP)-binding site of PI4K and PKG, paving the way for structure-based optimization of imidazopyridazines targeting both PI4K and PKG. Read More

Plants (Basel) 2020 Dec 8;9(12). Epub 2020 Dec 8.

Division of Genetics, ICAR-Indian Agricultural Research Institute, New Delhi 110012, India.

Breeding rice varieties with a low phytic acid (LPA) content is an effective strategy to overcome micronutrient deficiency in a population which consume rice as a staple food. An LPA mutant, Pusa LPA Mutant 11 (PLM11), was identified from an ethyl methane sulfonate (EMS)-induced population of Nagina 22. The present study was carried out to map the loci governing the LPA trait in PLM11 using an F population derived from a cross between a high phytic acid rice variety, Pusa Basmati 6, with PLM11. Read More