The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo–electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice. In addition, GS-6207 interferes with capsid binding to the cellular HIV-1 cofactors Nup153 and CPSF6 that mediate viral nuclear import and direct integration into gene-rich regions of chromatin. These findings elucidate structural insights into the multimodal, potent antiviral activity of GS-6207 and provide a means for rationally developing second-generation therapies.
Pathogenesis related (PR) proteins are one of the major sources of plant derived allergens. These proteins are induced by the plants as a defense response system in stress conditions like microbial and insect infections, wounding, exposure to harsh chemicals, and atmospheric conditions. However, some plant tissues that are more exposed to environmental conditions like UV irradiation and insect or fungal attacks express these proteins constitutively. These proteins are mostly resistant to proteases and most of them show considerable stability at low pH. Many of these plant pathogenesis related proteins are found to act as food allergens, latex allergens, and pollen allergens. Proteins having similar amino acid sequences among the members of PR proteins may be responsible for cross-reactivity among allergens from diverse plants. This review analyzes the different pathogenesis related protein families that have been reported as allergens. Proteins of these families have been characterized in regard to their biological functions, amino acid sequence, and cross-reactivity. The three-dimensional structures of some of these allergens have also been evaluated to elucidate the antigenic determinants of these molecules and to explain the cross-reactivity among the various allergens.
Tissue engineering and regenerative medicine are emerging as future approaches for the treatment of acute and chronic diseases. However, many challenging clinical conditions exist today and include congenital disorders, trauma, infection, inflammation and cancer, in which hard and soft tissue damage, organ failure and loss are still not treated effectively. Regenerative medicine has contributed to a number of innovations through artificial implants and biomedical materials, with advances are continually being made. Researchers are constantly developing new biomaterials and tissue engineered technologies to stimulate tissue regeneration in order to repair and replace damaged or malfunctioning organs. However, the challenge continues to lie in devising effective biomedical materials that can be implanted as scaffolds. Various approaches are emerging, according to the organ, tissue, disease and disorder. Scaffolds are implanted cell-free, or incorporated with stems cells, committed cells, or bioactive molecules. Irrespective, engineered biomaterials are required to regenerate and ultimately reproduce the original physiological, biological, chemical and mechanical properties over time. This is enabled by providing a three-dimensional architecture for cells to adhere, migrate, proliferate within, and differentiate appropriately for the growth of new tissues to provide a relevant structure, and in so doing, restore function. Biodegradable materials have been used extensively as regenerative therapies since their advent in early 20th century. One notable example is the development of surgical fixation devices. The selection, design and physicochemical properties of these materials are important and must consider biocompatibility, biodegradability and minimal cytotoxicity in the host to enable cell-proliferation, cell-matrix interactions and intercellular signalling for stimulating tissue growth. In this review, we critique the most studied and recently developed biodegradable
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