Nanodecoys for Antiviral Applications Against SARS-CoV-2 and Other Viruses

The COVID-19 pandemic caused by SARS-CoV-2 has driven the exploration of various mitigation strategies, including vaccines, antiviral drugs, and virus-neutralizing antibodies. However, the emergence of numerous viral variants has limited the effectiveness of these approaches, highlighting the need for innovative solutions. Among the promising technologies are cell membrane nanodecoys, which mimic susceptible cells and capture viruses through antigens on their surfaces. These nanodecoys offer a potential solution to viral mutations without exerting high selective pressure on the virus. Nevertheless, challenges in mass production and effective viral inactivation have hindered their broader application.

In this study, researchers developed sulfated liposome-based nanodecoys that mimic cell membrane glycocalyx, constructed from FDA-approved excipients, hydrogenated soybean phosphatidylcholine (HSPC), and cholesteryl sodium sulfate (CS). These nanodecoys not only bind to the spike proteins of the coronavirus through sulfate groups but also fuse with the viral envelope, leading to virus deformation and inactivation. The development of these nanodecoys aims to address the limitations of natural cell membrane nanodecoys, particularly in scalability and the ability to inactivate viral particles.

Physicochemical characterization of the nanodecoys revealed that their antiviral effectiveness depends on the size and composition of the liposomes. Smaller nanodecoys, approximately 40 nm in size, demonstrated superior antiviral activity compared to larger ones (about 100 nm), largely due to their higher surface area and enhanced binding capabilities. The antiviral properties were assessed using lentiviruses, which serve as a model for studying viral infection mechanisms. The study found that increasing the proportion of CS in the nanodecoys significantly enhanced their ability to neutralize and inactivate the virus, indicating the critical role of sulfate groups in binding the virus.

Further investigations into the mechanism of action showed that the nanodecoys operate by mimicking heparan sulfate proteoglycans (HSPGs), which are commonly used by viruses, including SARS-CoV-2, to attach to host cells. The sulfate groups on the liposomes interact strongly with viral spike proteins, enabling the nanodecoys to neutralize the virus by blocking its interaction with cells. Importantly, this binding can also induce membrane fusion, which deforms the viral structure and leads to permanent inactivation, preventing the virus from regaining infectivity.

The efficacy of these nanodecoys was also tested against multiple SARS-CoV-2 variants, such as Alpha and Delta, and other coronaviruses like HCoV-OC43. Results demonstrated that the nanodecoys effectively reduced infection rates across these diverse viral strains, underscoring their broad-spectrum antiviral potential. Notably, the nanodecoys were able to neutralize viruses at various concentrations, further validating their robustness and applicability in different therapeutic contexts.

PackGene played a pivotal role in this research by providing the AAV vectors, AAV packaging, and lentiviruses, which were crucial for evaluating the antiviral efficacy of the nanodecoys. These viral components enabled comprehensive testing of the nanodecoys’ performance against vectors that utilize mechanisms similar to significant viral pathogens, such as the SARS-CoV-2 virus.

Overall, the sulfated liposome-based cell membrane glycocalyx nanodecoys offer a scalable and effective approach to combating SARS-CoV-2 and other viruses. By combining bio-recognition and virus inactivation through membrane fusion, these nanodecoys address the limitations posed by viral mutations and offer a potent prophylactic measure against a broad range of viruses that utilize HSPG co-factors for entry. This innovative strategy not only enhances the antiviral arsenal against COVID-19 but also lays the groundwork for developing advanced theranostic antiviral nanosystems with combined bio-recognition and inactivation capabilities.

PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.

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