Delivery of a novel membrane-anchored Fc chimera enhances NK cell-mediated killing of tumor cells and persistently virus-infected cells.

Antibody-dependent cellular cytotoxicity (ADCC) is one of the most powerful mechanisms for Natural Killer (NK) cells to kill cancer cells or virus-infected cells. A novel chimeric protein (NA-Fc) was created, which when expressed in cells, positions an IgG Fc domain on the plasma membrane, mimicking the orientation of IgG bound to the cell surface. This NA-Fc chimera was tested with PM21-NK cells, produced through a previously developed particle-based method which yields superior NK cells for immunotherapeutic applications. Real time viability assays revealed higher PM21-NK killing of both ovarian and lung cancer cells expressing NA-Fc, which correlated with increased release of TNF-α and IFN-γ cytokines from NK cells and was dependent on CD16-Fc interactions. Lentivirus delivery of NA-Fc to target cells increased the rate of PM21-NK cell killing of A549 and H1299 lung, SKOV3 ovarian and A375 melanoma cancer cells. This NA-Fc-directed killing was extended to virus infected cells, where delivery of NA-Fc to lung cells that were persistently infected with Parainfluenza virus resulted in increased killing by PM21-NK cells. In contrast to its effect on PM21-NK cells, the NA-Fc molecule did not enhance complement mediated lysis of lung cancer cells. Our study lays the foundation for application of the novel NA-Fc chimera that could be delivered specifically to tumors during oncolytic virotherapy to mark target cells for ADCC by co-treatment with adoptive NK cells. This strategy would potentially eliminate the need to search for unique cancer specific antigens for development of new antibody therapeutics.

Potent Inactivation of Human Respiratory Viruses Including SARS-CoV-2 by a Photoactivated Self-Cleaning Regenerative Antiviral Coating.

The COVID-19 pandemic marks an inflection point in the perception and treatment of human health. Substantial resources have been reallocated to address the direct medical effects of COVID-19 and to curtail the spread of the virus. Thereby, shortcomings of traditional disinfectants, especially their requirement for regular reapplication and the related complications (e.g., dedicated personnel and short-term activity), have become issues at the forefront of public health concerns. This issue became especially pressing when infection-mitigating supplies dwindled early in the progression of the pandemic. In consideration of the constant threat posed by emerging novel viruses, we report a platform technology for persistent surface disinfection to combat virus transmission through nanomaterial-mediated, localized UV radiation emission. In this work, two formulations of Y2SiO5-based visible-to-UV upconversion nanomaterials were developed using a facile sol-gel-based synthesis. Our formulations have shown substantial antiviral activities (4 × 104 to 0 TCID50 units in 30 min) toward an enveloped, circulating human coronavirus strain (OC43) under simple white light exposure as an analogue to natural light or common indoor lighting. Additionally, we have shown that our two formulations greatly reduce OC43 RNA recovery from surfaces. Antiviral activities were further demonstrated toward a panel of structurally diverse viruses including enveloped viruses, SARS-CoV-2, vaccinia virus, vesicular stomatitis virus, parainfluenza virus, and Zika virus, as well as nonenveloped viruses, rhinovirus, and calicivirus, as evidence of the technology's broad antiviral activity. Remarkably, one formulation completely inactivated 105 infectious units of SARS-CoV-2 in only 45 min. The detailed technology has implications for the design of more potent, long-lived disinfectants and modified/surface-treated personal protective equipment targeting a wide range of viruses.

ALD based nanostructured zinc oxide coated antiviral silk fabric† † Electronic supplementary information (ESI) available. See https://doi.org/10.1039/d2ra02653h

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.2 stealth) has exacerbated the problem: again raising the issues of infection prevention strategies and the efficacy of personal protective equipment (PPE). Against this backdrop, we report an antimicrobial fabric for PPE applications. We have fabricated a nanofibrous silk-PEO material using electrospinning followed by zinc oxide thin film deposition by employing the atomic layer deposition technique. The composite fabric has shown 85% more antibacterial activity than the control fabric and was found to possess substantial superoxide dismutase–mimetic activity. The composite was further subjected to antiviral testing using two different respiratory tract viruses: coronavirus (OC43: enveloped) and rhinovirus (RV14: non-enveloped). We report a 95% reduction in infectious virus for both OC43 and RV14 from an initial load of ∼1 × 105 (sample size: 6 mm dia. disk), after 1 h of white light illumination. Furthermore, with 2 h of illumination, ∼99% reduction in viral infectivity was observed for RV14. High activity in a relatively small area of fabric (3.5 × 103 viral units per mm2) makes this antiviral fabric ideal for application in masks/PPE, with an enhanced ability to prevent antimicrobial infection overall. This study presents an antiviral self-cleaning fabric for masks/PPE applications with protection against human coronavirus.

ALD based nanostructured zinc oxide coated antiviral silk fabric.

The COVID-19 pandemic has underscored the importance of research and development in maintaining public health. Facing unprecedented challenges, the scientific community developed antiviral drugs, virucides, and vaccines to combat the infection within the past two years. However, an ever-increasing list of highly infectious SARS-CoV-2 variants (gamma, delta, omicron, and now ba.2 stealth) has exacerbated the problem: again raising the issues of infection prevention strategies and the efficacy of personal protective equipment (PPE). Against this backdrop, we report an antimicrobial fabric for PPE applications. We have fabricated a nanofibrous silk-PEO material using electrospinning followed by zinc oxide thin film deposition by employing the atomic layer deposition technique. The composite fabric has shown 85% more antibacterial activity than the control fabric and was found to possess substantial superoxide dismutase-mimetic activity. The composite was further subjected to antiviral testing using two different respiratory tract viruses: coronavirus (OC43: enveloped) and rhinovirus (RV14: non-enveloped). We report a 95% reduction in infectious virus for both OC43 and RV14 from an initial load of ∼1 × 105 (sample size: 6 mm dia. disk), after 1 h of white light illumination. Furthermore, with 2 h of illumination, ∼99% reduction in viral infectivity was observed for RV14. High activity in a relatively small area of fabric (3.5 × 103 viral units per mm2) makes this antiviral fabric ideal for application in masks/PPE, with an enhanced ability to prevent antimicrobial infection overall.

Complement Inhibitors Vitronectin and Clusterin Are Recruited from Human Serum to the Surface of Coronavirus OC43-Infected Lung Cells through Antibody-Dependent Mechanisms.

Little is known about the role of complement (C') in infections with highly prevalent circulating human coronaviruses such as OC43, a group of viruses of major public health concern. Treatment of OC43-infected human lung cells with human serum resulted in C3 deposition on their surfaces and generation of C5a, indicating robust C' activation. Real-time cell viability assays showed that in vitro C'-mediated lysis of OC43 infected cells requires C3, C5 and C6 but not C7, and was substantially delayed as compared to rapid C'-mediated killing of parainfluenza virus type 5 (PIV5)-infected cells. In cells co-infected with OC43 and PIV5, C'-mediated lysis was delayed, similar to OC43 infected cells alone, suggesting that OC43 infection induced dominant inhibitory signals. When OC43-infected cells were treated with human serum, their cell surfaces contained both Vitronectin (VN) and Clusterin (CLU), two host cell C' inhibitors that can alter membrane attack complex (MAC) formation and C'-mediated killing. VN and CLU were not bound to OC43-infected cells after treatment with antibody-depleted serum. Reconstitution experiments with purified IgG and VN showed that human antibodies are both necessary and sufficient for VN recruitment to OC43-infected lung cells-novel findings with implications for CoV pathogenesis.

Metal-Mediated Nanoscale Cerium Oxide Inactivates Human Coronavirus and Rhinovirus by Surface Disruption.

The COVID19 pandemic has brought global attention to the threat of emerging viruses and to antiviral therapies, in general. In particular, the high transmissibility and infectivity of respiratory viruses have been brought to the general public's attention, along with the need for highly effective antiviral and disinfectant materials/products. This study has developed two distinct silver-modified formulations of redox-active nanoscale cerium oxide (AgCNP1 and AgCNP2). The formulations show specific antiviral activities toward tested OC43 coronavirus and RV14 rhinovirus pathogens, with materials characterization demonstrating a chemically stable character for silver nanophases on ceria particles and significant differences in Ce3+/Ce4+ redox state ratio (25.8 and 53.7% Ce3+ for AgCNP1 & 2, respectively). In situ electrochemical studies further highlight differences in formulation-specific viral inactivation and suggest specific modes of action. Altogether, the results from this study support the utility of AgCNP formulations as high stability, high efficacy materials for use against clinically relevant virus species.