Developing a Sprayable Antiviral Coating in Response to the SARS-CoV-2 Pandemic

Author: JC Daniel Calso
Mentors: Robert H. Grubbs and Christopher B. Marotta 
Editor: Ann Zhu


The year 2020 was marked by the novel 2019 coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2. The virus’s deadliness is largely attributed to its highly infectious nature even in those who are asymptomatic. Although it is generally accepted that the best measure against coronavirus spread is a combination of social distancing and universal face mask usage1, the virus remains viable and infectious on hard surfaces for up to 72 hours. This raises concerns over SARS-CoV-2 fomite transmission2,3 (Fig. 1) through contaminated surfaces, which led to public stockpiling of Lysol wipes and gloves. Diligent sanitization of common surfaces is a necessary precaution against COVID-19, particularly as pathogenic transmission through surface contamination has already caused many general hospital-acquired infections4,5. However, because it is infeasible to continuously sanitize public surfaces such as handrails and doorknobs, we must work towards a solution to remediate the issue of surface contamination by viruses and other pathogens.

Figure 1: SARS-CoV-2 is known to spread primarily through an airborne route, but there remains the risk of fomite transmission. Source: Galbadage, T., Peterson, B. M. & Gunasekera, R. S. Does COVID-19 Spread Through Droplets Alone?

The Grubbs group has adapted previous research on a sprayable and long-lasting antibacterial coating to combat this fomite transmission. We wanted to explore 1) the ability of the coating to significantly reduce the viability of virus particles on a surface and 2) the adhesive properties of our coating and how these properties may be altered for a variety of surface types.

Our coating consists of quaternized ammonium polypropylene (QAPP), which is composed of several quaternary ammonium cations linked to a polymer backbone. These quaternary ammonium cations (QACs or “quats”) are found in common commercial disinfectants such as Lysol or BeerClean. Quats work by disrupting the lipid bilayer that surrounds viruses and bacteria. The mechanism depends on charged interactions between the cation and this bilayer, and it can be enhanced by the addition of a variably long side chain to the cation (Fig. 2). 

Figure 2: The general mechanism of quaternary ammonium cations. The permanent positive charge interferes with the lipid bilayer of a cellular membrane or viral envelope. Adding a long carbon chain to this functional group introduces a secondary mechanism known as intercalation, where the long carbon chain of the quaternary ammonium cation will be drawn to the internal hydrophobic environment of the membrane.

Our hypothesis is that the carbon chain of the QAPP is attracted to the internal hydrophobic section of the bilayer, effectively behaving like a sword that pierces the hydrophilic exterior. To test this prediction, we prepared several derivatives with varying carbon chain lengths and examined their physical characteristics and antiviral/antimicrobial properties. In other words, we evaluated the efficacy of medium-length molecular “swords” in comparison to longer molecular “spears.”

In addition to evaluating the antiviral properties of our QAPP compound, we investigated its inherent adhesion to common substrates and the effect of two siloxane additives as adhesion promoters. Siloxanes, or silanes, are coupling agents that serve as an interface between two normally incompatible materials such as metal and organic polymers6. They are well established for dental applications7 and general plastic manufacturing8. Consequently, we studied the effect of two commercial siloxanes on our compound’s ability to adhere to metal.


Evaluating Antibacterial and Antiviral Capability 

Synthesis of the QAPP compound is a modular three-step, two-pot reaction (Fig. 3). This allows for a customizable synthetic procedure and variation of the carbon chain lengths on the quaternary ammonium cation. As previously stated, we wanted to investigate how the length of the carbon chain may influence the compound’s antiviral activity. The modularity of our procedures allowed for a total of seven derivatives to be synthesized: C6, C8, C10, C12, C14, C16, and C18.

Figure 3: The general synthetic scheme for quaternized amino propylene (QAPP). Structures of reagents are provided. Note that the final carbon chain of our target QAPP compound may be selectively synthesized by choosing an appropriate alkyl bromide for step 2. Adapted from US20180362714A1

Although time intensive, the synthetic procedure is relatively simple and the starting material is readily available. Chlorinated polypropylene (CPP) is coupled with branched polyethyleneimine (B-PEI), which is then alkylated (Step 2 of Fig. 3). This step demonstrates the customizability and modularity of the synthetic procedure: we select a specific alkyl bromide based on our target chain length for the final QAPP. For example, the C6 derivative necessitated hexyl bromide (C6H13Br), the C12 derivative necessitated dodecyl bromide (C12H25Br), etc. From here, the new aminated polypropylene intermediate (APP) is once again alkylated to produce crude QAPP. The identity of the alkyl bromide in this step (R’X in Fig. 3) does not depend on our target derivative; we opted for methyl iodide in most of our syntheses. Crude QAPP must undergo a series of washing and precipitating to be purified; purification can be quite challenging, especially with longer chain derivatives. As the chain lengths get longer, hydrophobic interactions increase the viscosity of the material. The shorter chain lengths (C6, C8, C10) behave more like oil, whereas longer chain lengths (C14, C16) start to behave like gummy clay. 

Polypropylene discs treated with our QAPP derivatives were sent to external companies and collaborators for antiviral and antibacterial testing. Samples of the C6, C12, and C14 derivatives were sent to the Jason Debley Group at Seattle Children’s Research Institute to be tested against SARS-CoV-2; all of our derivatives (C6, C8, C10, C12, C14, C16, and C18) were sent to Spectral Platforms Inc. to be tested for their antibacterial abilities; and samples of C12 and C14 were sent to Microchem Laboratory in Texas to be tested against an alternative, similar strain of the human coronavirus. 

Preliminary results of antiviral tests from the Debley group and Microchem Labs found no antiviral activity in our C12 and C14 derivatives, and we currently await antiviral results for our C6 derivative. Antibacterial results from Spectral Platforms, however, suggest significant activity against E. coli and S. epidermidis in the C6 and C8 derivatives. Moreover, this antibacterial activity decreases with the longer chain length derivatives.

Evaluating Antibacterial and Antiviral Capability

While synthesizing and testing our QAPP compounds, we also wanted to explore our derivatives’ innate adhesion to common surfaces. Adhesion tests were conducted according to the protocol prescribed by the American Society of Testing and Materials (ASTM), commonly referred to as “the tape test.”9 It is generally used as a field test for evaluating painted surfaces, and it served us well, because it could be easily adapted to public health restrictions requiring remote work. The protocol requires minimal equipment and is simple to perform: the operator cuts a grid into the coating, applies and quickly removes tape from the grid, then grades the adhesive on a 0-5 scale based on the provided chart (Fig. 4). With this scale of increasing adhesion, a low percentage removal of the adhesive material by the tape would correspond to a high adhesive performance score of 5.

Figure 4: A grading scale for tape test results from ASTM D3359 Method B (left) with representative results of our QAPP products and their subjective scores (right). Note the overlap and lack of precision in grading the middle two samples, which inspired us to formalize this procedure with image analysis software. 

The ASTM grading process is inherently subjective, so we modernized it with ImageJ to minimize operator bias. High resolution photos were taken of the coating before and after the tape test. Using ImageJ software, we “thresholded” these images; ImageJ allowed us to select and calculate the areas without coating on the grid. Initially, thresholding was done manually using color qualities to highlight what “looked right,” risking subjectivity and operator error. So, we automated the protocol for greater efficiency and decreased subjectivity. ImageJ has a built-in command “Difference” that can merge before and after images and highlight only the differences between the two. This streamlined our thresholding, and enabled us to assign standardized and accurate percentages to the degree of removal for the material. 

Figure 5 demonstrates the process and evolution of our ImageJ protocol. Subjectively, the sample may be given a score of 2 or 3 based on the post-test image alone (Fig. 5B). The initial ImageJ protocol worked well, but was still subjective and slightly overstated the amount of material removed (Fig. 5C). The final protocol accurately graded the material by excluding the lattice lines and only highlighting areas that truly changed (Fig. 5D). 

Figure 5: A representative analysis of C6 on polypropylene. The lattice pattern is cut into the sample (A). Tape is applied, pulled off, and the surface examined for removed coating (B). The initial ImageJ protocol involved manually thresholding of net change in  (C, in red) before the process was refined for precise measurements of only the area affected by tape (D, in black). Note that the grid lines are included as part of the calculations in the initial protocol (C) but not included in the refined protocol (D).

Two rounds of adhesion testing were conducted: one compared three QAPP derivatives on plastic discs, and the other compared the effect of the siloxane additives on our compounds’ adhesion to metal surfaces common to public and hospital settings. In the first round of tests, two equal weights of C6 and C14 and a lighter weight deposition of C6 were compared on the basis of their adhesion to a plastic disc. The C14 sample adhered the best out of all three samples and was the only sample to score a 5 on the ASTM scale. The higher weight C6 sample had the lowest adhesion score of 0, while the lower weight C6 sample surprisingly performed slightly better, scoring a 2. (Fig. 6

Figure 6: Derivative performance against two adhesion strengths of tape. Lower values relate to stronger adhesion to the surface. The right axis indicates the corresponding ASTM score that would be assigned to that particular tape test. 

For aluminum and stainless steel, a low weight of the C6 QAPP was used when comparing the effects of the siloxane additives. We also tested the additive effects on a C14 derivative on aluminum substrate. Results were less distinct: in all tests, less than 5% of material was removed and all samples scored a 5 both with or without an additive (Table 1). 

Given low percentage removals without adhesion promoters, our compound appears to have an innate adhesion to metal surfaces and does not require modification.

Table 1 Results of material removed. QAPP derivatives with various additives on aluminum and stainless-steel vs 57 oz tape.


Many of the QAPP compound’s physical characteristics are heavily influenced by the length of its carbon chain. As the carbon chain length increases, hydrophobicity of the coating increases. These hydrophobic chains were predicted to be attracted to the hydrophobic component of the viral envelope; however, it is very likely that the carbon chains are also attracted to each other to the extent that they aggregate as they dry. This aggregation makes the compound difficult to wet evenly onto a substrate. Further, we observed long chain derivatives forming interrupted and lamellar surfaces while the short chain derivatives formed smooth, even surfaces (Fig. 7).

Figure 7: C14 (top) and C6 (bottom) on aluminum. Hydrophobic interactions in C14 may be causing the lamellar surface instead of the smooth surface found in C6; these hydrophobic interactions may also interfere with the compound’s antiviral properties.

Critically, the aggregation likely interferes with the antiviral properties of our QAPP compound. Aggregation may “shield” the charged functional ammonium cation from interacting with a virus’s lipid bilayer. The long carbon chains are also not free to insert themselves into the viral membrane, intercalating with each other. Hydrophobic interactions may also interfere with antimicrobial activity by repelling the aqueous droplets that carry viral and bacterial loads, similar to how a freshly waxed car repels water, causing it to bead up and minimize surface contact. Most QAC-based sanitizers require that a surface remains wet with the solution before being wiped clean. Monomeric QACs with long side chains may work well in a dilute aqueous environment where they are more likely to interact with cellular or viral envelopes, but our coating’s application in dry environments may favor shorter chain derivatives. This hypothesis is preliminarily supported by the antibacterial activity present in the shortest C6 derivative. It is worth noting that the theoretical mechanism of antimicrobial QACs is nonspecific i.e., it does not target one virus or bacteria over the other, so we hope to see similarities between our antibacterial and antiviral test results.

The strong hydrophobic interaction within the compound is believed to contribute to durability and adhesion promotion. The C14 sample adhered strongly to the plastic square and resisted removal, possibly due to the long chains’ intercalation into other QAPP molecules and the plastic surface, creating a high molecular weight surface shell. Despite being a shorter carbon chain, the lighter C6 sample is believed to have benefited from this same effect, whereas the heavier C6 sample suffered in terms of adhesion, possibly due to a stronger self-attraction. Our data suggests that there exists a potential balance between high sample weight and carbon chain length. 

Overall, our QAPP compound seems to possess an inherent adhesion to common materials such as plastic, aluminum, and stainless steel. The specific percentages calculated when comparing the effects of silane additives are not distinct enough from each other (Table 1) to conclude a positive or negative effect of silane additives to our QAPP compound. Future tests should be performed to examine the effect of the same silane additives on the high weight C6 derivative on polypropylene, since it performed poorly without any additives. 


In response to the worldwide SARS-CoV-2 pandemic of 2020, we aimed to develop a long-lasting, spray-on antiviral coating. As we await definitive results of antiviral activity, we have seen preliminary antibacterial activity from one of our derivatives. We have investigated this derivative’s adhesive properties and have found it to adhere well to common surfaces such as polypropylene, stainless steel, and aluminum. For future studies on adhesion, we have developed a protocol based on an industry standard that produces consistent data with high precision. 

Further directions for this project are also currently in consideration. Chain lengths even shorter than the C6 derivative may be explored, adding a wonderful dagger to our “sword vs spear” analogy. We will also continue performing adhesion tests to better understand how our coating may be applied to the variety of contact surfaces in the public sphere; we want to ensure its durability and viability to work on a long-term scale. Given our C6 derivative’s antibacterial activity and innate adhesion to a variety of surfaces, we see the value of our derivative not only in addressing the viral pandemic, but also in treating common surfaces in hospital settings. Antibacterial tests will continue to be utilized, as it is much easier to test a compound against bacteria rather than viruses—particularly pandemic-causing viruses. We are optimistic about our product, and hope it will assist in protecting frontline medical workers and the general public.


This project was part of a SURF/WAVE session that was altered due to the pandemic conditions of 2020 and was only possible due to the support and creativity of special individuals. I would like to thank the Grubbs Group, especially Professor Robert H. Grubbs and Dr. Christopher B. Marotta, for welcoming me and adapting assignments that allowed me to contribute from home. I would like to warmly thank the Student-Faculty Programs Office for their tenacity in continuing the 2020 SURF session and showing creativity in hosting a virtual summer research program. Special thanks to the Merkin Institute for their COVID-19 Challenge grant that initiated the project, as well as Genentech for sponsoring my WAVE research session. Finally, additional thanks go to the Jason Debley Research Group and Spectral Platforms Inc. for testing for our compounds’ antiviral (Debley) and antibacterial (Spectral) activity.


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