Adv Protein Chem Struct Biol
May 2024
The immune system is complicated, interconnected, and offers a powerful defense system that protects its host from foreign pathogens. Immunotherapy involves boosting the immune system to kill cancer cells, and nowadays, is a major emerging treatment for cancer. With the advances in our understanding of the immunology of cancer, there has been an explosion of studies to develop and evaluate therapies that engage the immune system in the fight against cancer.
View Article and Find Full Text PDFThe RNA-dependent RNA polymerase (RdRp) complex of SARS-CoV-2 lies at the core of its replication and transcription processes. The interfaces between holo-RdRp subunits are highly conserved, facilitating the design of inhibitors with high affinity for the interaction interface hotspots. We, therefore, take this as a model protein complex for the application of a structural bioinformatics protocol to design peptides that inhibit RdRp complexation by preferential binding at the interface of its core subunit nonstructural protein, nsp12, with accessory factor nsp7.
View Article and Find Full Text PDFThe development of monoclonal antibody (mAb) biosimilars is a complex process. The key to their successful development and commercialization is an in-depth understanding of the key product attributes that impact safety and efficacy and the strategies to control them. Functional assessment of mAb is a crucial part of the comparability of biopharmaceutical drugs.
View Article and Find Full Text PDFChronic hepatitis B virus (HBV) infection is a global problem. The loss of hepatitis B surface antigen (HBsAg) in serum is a therapeutic end point. Prolonged therapy with nucleoside/nucleotide analogues targeting the HBV-polymerase may lead to resistance and rarely results in the loss of HBsAg.
View Article and Find Full Text PDFLong-term stability of therapeutic monoclonal antibody (mAb) products is necessary for their successful commercialization. Freeze-thaw (F/T) operations are often performed for a mAb product during processing, storage and distribution. Lyophilization (Lyo) is another unit operation that is commonly used for drug product manufacturing of mAbs.
View Article and Find Full Text PDFMonoclonal antibody (mAb) products are presently the dominant class of therapeutic proteins. When stressed, they are known to be prone to molecular instabilities like aggregation, fragmentation, oxidation and reduction, of which aggregation is typically the most significant concern. These stresses may be experienced during manufacturing, storage, filling, formulation development and shipping.
View Article and Find Full Text PDFWe report a structure-based approach to design peptides that can bind to aggregation-prone, partially folded intermediates (PFI) of insulin, thereby inhibiting early stages of aggregation nucleation. We account for the important role of the modular architecture of protein-protein binding interfaces and tertiary structure heterogeneity of the PFIs in the design of peptide inhibitors. The determination of association hotspots revealed that two interface segments are required to capture majority contribution to insulin homodimer binding energy.
View Article and Find Full Text PDFBiosimilars are products that are similar in terms of quality, safety, and efficacy to an already licensed reference/ innovator product and are expected to offer improved affordability. The most significant source of reduction in the cost of development of a biosimilar is the reduced clinical examination that it is expected to undergo as compared to the innovator product. However, this clinical relief is predicated on the assumption that there is analytical similarity between the biosimilar and the innovator product.
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