Prolonged Surface-Based Antiviral Measures to Combat SARS-CoV-2 and Future Pandemic Preparedness

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The coronavirus disease (COVID-19), resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a public health emergency of international concern in early 2020. The disease, which emerged in Wuhan, China, quickly escalated from a regional outbreak to a global health crisis, leading the World Health Organization (WHO) to recognize it as a global pandemic on March 11, 2020. The highly contagious nature of SARS-CoV-2, coupled with rapid mutation patterns and adaptive capabilities, has rendered the global response exceptionally challenging. This response has been compounded by the complex nature of the virus itself, its modes of transmission, and the need for sustainable, efficient antiviral measures across both public and private spaces.

By early 2020, it had become clear that SARS-CoV-2 spreads primarily through human-to-human transmission. The primary modes of transmission were identified as respiratory droplets expelled during coughing, sneezing, and talking, which can travel through the air and settle on various surfaces, where they remain viable for varying lengths of time. Studies have shown that at ambient temperatures, SARS-CoV-2 can survive on plastics and stainless steel surfaces for 3 to 4 days, on glass for up to 48 hours, and on cardboard for as long as 24 hours.

This high resilience on surfaces has added a substantial layer of complexity to pandemic management, underscoring the importance of effective surface disinfection protocols to mitigate indirect transmission risks. Touching contaminated surfaces and subsequently touching the eyes, nose, or mouth has been identified as a major vector of SARS-CoV-2 transmission, with humans shown to touch their faces up to 200 times per day. Such findings highlight the critical need for antiviral surface treatments that are not only effective but also capable of maintaining their efficacy over extended periods.

As part of the early response, numerous disinfectants were adopted globally to mitigate virus transmission via surface contamination. The Environmental Protection Agency (EPA) authorized various disinfectant categories, including quaternary ammonium compounds, peroxides, alcohol-based solutions, and phenol-based compounds. These disinfectants have demonstrated efficacy against SARS-CoV-2, primarily by targeting and disrupting its lipid bilayer envelope. However, many of these compounds lack lasting antiseptic properties and require frequent reapplication, particularly in high-traffic areas.

Furthermore, the potential toxicity associated with excessive disinfectant use raised concerns about respiratory health, skin irritation, and environmental pollution. For example, frequent exposure to quaternary ammonium compounds has been associated with asthma and other respiratory conditions in both healthcare workers and the general population. Additionally, environmental runoff from disinfectants has been shown to introduce phenols and other toxic compounds into water systems, thereby disrupting aquatic ecosystems.

To address these issues, researchers began exploring advanced surface treatments that could provide long-term antiviral protection without frequent reapplication. This pursuit has given rise to two primary categories of surface-based antiviral strategies: contact-based and release-based systems. Contact-based systems operate by covalently bonding active antiviral agents to the surface, effectively preventing agent depletion over time. However, the antiviral efficacy of these systems can be somewhat limited, as covalently bound agents may lose reactivity relative to their free counterparts. Release-based systems, in contrast, allow active agents to be non-covalently attached to surfaces, enabling them to release gradually over time. While these systems can provide highly effective, sustained antiviral action, the agents eventually deplete, necessitating periodic replenishment.

In an effort to optimize both longevity and efficacy, some researchers have pursued hybrid systems that combine covalently and non-covalently attached agents. In a prominent study by Druvari et al., copolymers of poly(4-vinylbenzyl chloride-co-acrylic acid) and poly(sodium 4-styrenesulfonate-co-glycidyl methacrylate) were modified with both covalent and electrostatic biocides, specifically targeting viruses like SARS-CoV-2. The results of this research suggested that systems with combined attachment methods could strike a beneficial balance between high efficacy and sustained antiviral action.

The system with the electrostatically bound biocide displayed significant activity against pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, but surfaces containing both covalently and non-covalently bound agents achieved the most favorable results overall. Such advancements underscore the promise of mixed-mode surface treatments for applications in healthcare settings, transportation hubs, and other areas of high human contact.

Despite these advancements, few biocidal surfaces have been tested for direct activity against SARS-CoV-2 itself. Those that have been developed primarily employ release-based mechanisms and are composed of negatively charged polymers coupled with electrostatically bound cationic surfactants. These surfactants, including commonly used compounds like cetylpyridinium chloride, have demonstrated activity against a range of bacteria and enveloped viruses by disrupting lipid bilayers. Recent studies have focused on creating polymer-surfactant complexes, such as those involving polystyrene sulfonate with benzalkonium chloride (BAC), which have shown promising anti-SARS-CoV-2 properties. However, to date, no coatings incorporating both covalently and non-covalently bound virucidal agents specifically against SARS-CoV-2 have reached widespread implementation. Researchers are currently investigating whether the addition of non-covalent agents in combination with covalently bound agents can achieve a superior, long-lasting antiviral efficacy tailored to prevent SARS-CoV-2 transmission.

Surface microstructure plays an equally significant role in antiviral efficacy, particularly in enhancing or inhibiting virus attachment. Hydrophobic and structured surfaces have been found to prevent virus attachment by reducing the available contact area. Additionally, structured surfaces may help trap viral particles in micro-scale depressions, limiting viral spread upon initial contact. Some researchers have pursued approaches that combine the benefits of micro-structuring with chemical modifications, aiming to create coatings that repel viral attachment while simultaneously delivering high antiviral efficacy. However, the optimal surface structure and the impact of roughness on the activity of combined covalent and non-covalent systems against SARS-CoV-2 remain under investigation.

The following research aims to analyze and validate surfaces that exhibit specific antiviral properties against SARS-CoV-2 based on the integration of contact-based and release-based mechanisms. Furthermore, the comparative activity of flat and structured surfaces is explored to determine the influence of surface morphology on antiviral efficacy. To impart covalent antiviral action, surfaces were modified using dimethyloctadecyl [3-(trimethoxysilyl)propyl]ammonium chloride (DTSAC), a cationic agent with a hydrophobic tail resembling those found in many common disinfectants. For release-based action, benzalkonium chloride (BAC), a widely used quaternary ammonium disinfectant, was non-covalently attached to surfaces. Additionally, the newly synthesized cationic gemini surfactant, N1,N1,N4,N4-tetrakis(2-hydroxyethyl)-N1,N4-di((Z)-octadec-9-enyl)butane-1,4-diaminium bromide (C18-4-C18), was tested as a potential alternative to BAC. By incorporating elongated nanoparticles (NPs) on structured surfaces, the study aimed to assess whether surface roughness would impact antiviral efficacy by providing increased surface area for virus-agent interaction.

The resulting coatings were analyzed for their ability to inactivate SARS-CoV-2, both in terms of rapid efficacy (within 5 minutes) and over extended periods of exposure. Initial tests demonstrated that coatings combining covalently and non-covalently bound disinfectants showed significantly enhanced antiviral activity against SARS-CoV-2, compared to those with only covalently bound agents. The findings suggest that combining contact- and release-based actions in a single surface modification could be key to achieving high, sustained efficacy across a range of public and clinical environments.

Advanced Surface Technologies for Sustained SARS-CoV-2 Inactivation: Innovations, Efficacy, and Public Health Applications

COVID-19’s viral transmission dynamics have compelled an ongoing investigation into materials and environmental hygiene methods with the potential to offer sustained protection against SARS-CoV-2. With the rapid adaptation of the virus, especially through mutations, one of the most complex challenges has been developing materials and disinfection methods that retain efficacy against varied virus forms. Recent insights suggest that surface coatings optimized with antiviral agents need not only to be efficient but also robust against SARS-CoV-2’s mutational evolution. This requirement has intensified interest in multifunctional surfaces and layered disinfection protocols that can neutralize a broader range of SARS-CoV-2 variants.

Understanding the molecular behavior of SARS-CoV-2 has been fundamental in designing long-lasting antiviral materials. Each structural protein of SARS-CoV-2—such as the spike (S) protein, the envelope (E) protein, the membrane (M) protein, and the nucleocapsid (N) protein—plays a distinct role in both infectivity and resilience on surfaces. The S protein, responsible for host cell binding via the ACE2 receptor, has been a focal point in surface-level disinfection research due to its sensitivity to specific biocidal compounds. Targeted inactivation of the S protein could potentially reduce surface transmissibility, but evidence suggests that a multifaceted approach targeting all proteins offers more consistent results.

Parallel to molecular insights, quantitative data on the durability of SARS-CoV-2 on various surfaces has refined disinfection strategies. For instance, recent data from studies conducted in ambient and fluctuating humidity levels demonstrate that higher humidity may accelerate viral degradation on certain materials, whereas dry conditions tend to prolong viral viability on surfaces like plastic and stainless steel. Ambient temperature changes have shown a lesser but still significant impact, with extreme temperatures reducing viral stability, while moderate indoor conditions seem to favor virus survival. Research continues to delve into these parameters to enhance material design.

The choice of surface material composition directly influences antiviral effectiveness. Notably, metals and polymers have become primary materials in SARS-CoV-2 research. Copper alloys, for example, have been validated as potent antiviral surfaces due to their ability to disrupt viral proteins and RNA through ion release, a feature that distinguishes them from other metals. Studies indicate that copper ions generate reactive oxygen species (ROS) upon contact with viral particles, effectively damaging the viral envelope and genome. In contrast, silver nanoparticles (AgNPs), long investigated for their broad-spectrum antimicrobial properties, are now showing promise against SARS-CoV-2. Silver’s interaction with viral proteins, particularly through Ag+ ion release, causes structural deformations within the virus, making it a viable option for multi-use antiviral surfaces. Further studies are needed to compare the specific interactions of silver ions and copper ions in neutralizing SARS-CoV-2 under various environmental conditions.

Polymers, particularly those modified with antiviral agents, are undergoing trials for their potential to retain active agents and release them gradually. Quaternary ammonium compounds, previously used in various applications for their antimicrobial qualities, have been adapted within polymers to maintain viral inactivation over prolonged periods. Polymers functionalized with biocides have shown a capacity to release active compounds at slower rates, extending protection against virus adherence and transmission. Advanced manufacturing techniques, such as electrospinning, are being applied to embed quaternary ammonium compounds within polymer fibers, providing an additional layer of protection and flexibility in antiviral applications. Electrospun fibers have demonstrated consistent efficacy against enveloped viruses, making them a promising area for exploration in SARS-CoV-2 applications.

The most recent development in virus-resistant materials is the combination of self-cleaning and antiviral properties, designed for surfaces exposed to frequent human contact. Titanium dioxide (TiO2) coatings, widely known for their self-cleaning and photocatalytic abilities, are being tested against SARS-CoV-2. Under ultraviolet (UV) light, TiO2 releases ROS that interact with viral particles, effectively disrupting the viral membrane. When applied to high-touch surfaces in healthcare and transit settings, TiO2 has demonstrated promising results in reducing viral load. However, the practical application is challenged by the need for UV light activation, which restricts the use of TiO2 coatings to controlled environments or areas equipped with UV-C lighting.

Alongside TiO2, zinc oxide (ZnO) nanoparticles have garnered attention due to their broad-spectrum antiviral activity. ZnO functions similarly to TiO2 by generating ROS, but unlike TiO2, it does not require UV light activation, making it more adaptable for broader applications. Researchers are exploring ZnO coatings on frequently touched surfaces, such as elevator buttons and public touchscreens, due to ZnO’s robust antiviral efficacy in ambient light. Testing on ZnO’s long-term activity against SARS-CoV-2, along with its stability in high-traffic areas, is expected to clarify its potential for widespread use.

Additional measures under investigation include the use of graphene-based materials for antiviral surface applications. Graphene’s unique structural properties allow for a high degree of customization, enabling the functionalization of its surface with various antiviral agents. Graphene oxide, in particular, has shown effectiveness against bacteria and viruses, suggesting potential applications against SARS-CoV-2. Studies are ongoing to optimize graphene oxide’s surface functionalization to maximize its interaction with SARS-CoV-2 particles, with initial findings showing promise for integrating graphene-based materials in public spaces and healthcare environments.

The application of biocidal coatings to hospital fabrics and equipment surfaces has also become an area of interest, especially as hospitals are high-risk environments for surface transmission. Antiviral fabrics treated with chitosan, a biopolymer derived from chitin, have shown potential for reducing surface virus transmission. Chitosan, which disrupts viral membranes, is being investigated for use in personal protective equipment (PPE) and hospital curtains. Due to its biocompatibility and low toxicity, chitosan-treated surfaces offer a safe alternative for antiviral measures in patient areas.

It is essential to acknowledge the ongoing efforts to evaluate and refine the safety of these antiviral surfaces, particularly those employing nanomaterials. Regulatory bodies, such as the Environmental Protection Agency (EPA) and the European Medicines Agency (EMA), are actively involved in assessing the potential toxicity of prolonged exposure to surfaces treated with metal ions and nanoparticles. Rigorous safety evaluations are being conducted to ensure that antiviral surfaces do not introduce new health risks, especially for surfaces that come into frequent contact with skin or are used in confined environments with limited airflow.

Emerging research on environmental stability and effectiveness is contributing to a framework for integrating antiviral surfaces in the public and private sectors. An interdisciplinary approach that includes virology, material science, and environmental health is proving necessary to comprehensively address the complexities of SARS-CoV-2 transmission and mitigation. With new variants continuing to emerge, adaptability in antiviral surface technology remains crucial.


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