Treating paroxysmal nocturnal hemoglobinuria with humanized IgG 2/4 kappa antibody: understanding the ravulizumab structure

Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disease caused by somatic mutations in hematopoietic stem cells. As molecular studies are essential for a better understanding of new drugs, tools such as the international ImMunoGeneTics information system® are powerful approaches to better understanding the molecular conformations, arrangements, and orientations of two-dimensional (2D) structures of PNH treatments. This review aims to characterize the structure of Ravulizumab, describe its drug design process, and show its amino acid sequence through IGMT Colliers de Perles. Methods: The IMGT/mAb-DB interface was used to evaluate therapeutic antibodies and to clarify their immunological applications and pharmacological effects. Results: Ravulizumab binds to C5 and blocks its activation by complement pathway convertases, thereby preventing the release of the proinflammatory C5a and activation of the terminal pathway. The healthcare cost of PNH patients decreased because smaller doses of RAVUL could promote full complement blockage, maintaining the therapeutic effect. Choosing the epitope, hinge, and Fc region is crucial to balance efficacy and undesirable effects. The better intermolecular interactions of RAVUL with binding sites are due to its nanostructure design. Conclusion: These results bridge the gap between linear amino acid sequences and 3D structures. It may guide the development of new drugs for rare diseases.