Redox Active Antioxidant Nanozymes as Potential Antithrombotic and Antiviral Agents

Abstract

Reactive oxygen species (ROS), such as superoxide (O2-) hydrogen peroxide (H2O2), and hydroxyl radicals (.OH), generated as a result of cellular metabolism, play a multitude of physiological roles. They play key roles in signal transduction, pathogen defense, vascular tone regulation, angiogenesis, gene expression, and programmed cell death. The physiological levels of ROS are controlled by antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). However, excessive amounts of ROS act as the primary modulator of cellular dysfunction, promoting disease pathophysiology. Thrombosis is one of the pathological conditions where the effect of ROS on platelets plays a major role. The ROS-mediated activation and subsequent aggregation of platelets contribute to the progression of disease and development of thrombotic complications. Therefore, the inhibition of platelet aggregation is important for the prevention and treatment of various thrombotic disorders. As GPx is known to prevent platelet-dependent thrombosis, we have studied the effect of GPx mimetic antioxidant nanozymes for their ability to inhibit platelet activation and aggregation. We demonstrate that V2O5 nanozymes with specific, morphology-dependent GPx-like activity effectively inhibit physiological agonist-induced platelet aggregation in human platelets. The GPx-mimetic nanozymes modulate many events associated with platelet activation and aggregation such as elevated ROS and Ca2+ levels, P-selectin surface expression, ATP release, fibrinogen receptor activation, thrombin-induced TXA2 generation, and platelet-fibrinogen interactions. Our in vivo studies demonstrated that the V2O5 nanozyme effectively prevent pulmonary thromboembolism in mice. The nanozyme does not lead to the unwanted side effect of bleeding, which is important in the development of more effective and safe antithrombotic agents. ROS is also associated with many viral infections, including HIV and COVID-19. The levels of antioxidant enzymes are significantly altered during these viral infections. In this study, we have investigated the effect of an SOD mimetic CeVO4 nanozyme in suppressing HIV-1 reactivation and SARS-CoV-2 infection, the causative agents of Acquired Immunodeficiency Syndrome (AIDS) and the COVID-19 pandemic, respectively. The treatment with the SOD mimetic CeVO4 nanozyme significantly reduced both HIV-1 and SARS-CoV-2 infections in the cellular models. This study highlights the potential applications of SOD mimetic nanozymes in mitigating viral infections such as AIDS and COVID-19.