Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases

Advances in Nanotechnology as a Potential Alternative for Plant Viral Disease Management

Plant viruses cause enormous losses in agricultural production accounting for about 47% of the total overall crop losses caused by plant pathogens. More than 50% of the emerging plant diseases are reported to be caused by viruses, which are inevitable or unmanageable. Therefore, it is essential to devise novel and effective management strategies to combat the losses caused by the plant virus in economically important crops. Nanotechnology presents a new tendency against the increasing challenges in the diagnosis and management of plant viruses as well as plant health. The application of nanotechnology in plant virology, known as nanophytovirology, includes disease diagnostics, drug delivery, genetic transformation, therapeutants, plant defense induction, and bio-stimulation; however, it is still in the nascent stage. The unique physicochemical properties of particles in the nanoscale allow greater interaction and it may knock out the virus particles. Thus, it opens up a novel arena for the management of plant viral diseases. The main objective of this review is to focus on the mounting collection of tools and techniques involved in the viral disease diagnosis and management and to elucidate their mode of action along with toxicological concerns