Highly Sensitive, Engineered Magnetic Nanosensors to Investigate the Ambiguous Activity of Zika Virus and Binding Receptors

Abstract

The aim of this research is twofold: 1) to shed light on zika’s binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.

Zika: An emerging disease requiring prevention and awareness

“…Nanotechnology may already be providing some insights into the cross-reaction of antibodies in flaviviruses. One study utilized the antibody to antigen relationship, focusing specifically on an anti-Zika IgG monoclonal antibody (Z-ab) by using functionalized nanoparticles (MRNPs) with Z-ab [ 15 ]. The study indicates that there is multiple receptor binding between the full-length ZIKV envelope protein (ZENV) with AXL, HSP70, and TIM-1 [ 15 ].…”

“…One study utilized the antibody to antigen relationship, focusing specifically on an anti-Zika IgG monoclonal antibody (Z-ab) by using functionalized nanoparticles (MRNPs) with Z-ab [ 15 ]. The study indicates that there is multiple receptor binding between the full-length ZIKV envelope protein (ZENV) with AXL, HSP70, and TIM-1 [ 15 ]. This is potentially significant in understanding the cross-reactivity of ZIKV, given that AXL is a well-known receptor for flaviviruses [ 16 ], HSP70 has been specifically linked to the flavivirus causing neurotropism in Japanese encephalitis [ 17 ], and TIM-1 has been shown to be a receptor for both DENV and Ebola [ 15 ].…”

“…On the molecular level, understanding the virus—including structure, replication, and transmission—is essential. New research points to the binding and entry stage as vital to ZIKV propagation [ 15 ]. In the study conducted by Shelby and colleagues, favored binding sites for ZIKV were indicated using an innovative magnetic relaxation technology.…”

Nano-based approach to combat emerging viral (NIPAH virus) infection

“…Presently the direct use of MNP as an antiviral agent has been evaluated against Bacteriophages such as MS2 and other highly infectious viruses like zika virus, HCV, H5N2 (Table 1). [69][70][71][72] There have been many other findings of exploiting MNPs but their application in hybridized form is much more appreciated, which is described later under Hybrid nanoparticles (Table 3).…”

An Update on Sexual Transmission of Zika Virus

“…TIM and additional Tyro3-AXL-Mertk (TAM) family receptors (Tyro3) mediate the ZIKV entry into skin fibroblasts, endothelial cells and retinal cells [ 23 , 34 , 35 ]. Recently, in vitro binding assays have confirmed a significant degree of binding between Zika envelope protein (ZENV) and both TIM-1 and heat shock protein 70 kDa HSP70 [ 36 ]. However, incubation of Sertoli cells with blocking antibodies against AXL reduces viral infection, while inhibition of TIM-1 and TIM-4 receptors, and TAM receptors (Tyro3 and Mertk) did not significantly affect viral replication [ 28 ].…”