An ideal disinfectant should deactivate a broad range of viruses without harming users, says Dr Xian Jun Loh.

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Finding the ideal disinfection agent

7 Aug 2020

Regular disinfection can help to limit the spread of viral infections such as COVID-19, but only if carried out appropriately, write Xian Jun Loh and colleagues.

Viral outbreaks have posed severe threats to human health and well‐being throughout history. The novel coronavirus SARS‐CoV‐2, which was first reported by China in late 2019, has led to the largest coronavirus outbreak in the past two decades and also caused widespread socioeconomic disruption.

While government interventions can influence the rates and range of viral outbreaks, individuals can play equally—or arguably even more—important roles in limiting its spread. As viral transmissions occur via close human‐to‐human contact or through contact with contaminated surfaces, the use of sanitizing agents for personal care and surface disinfection can help to limit viral transmissions by inactivating the viruses before they have a chance to enter the human body.

In a review published in the journal View, titled “Sanitizing agents for virus inactivation and disinfection,” my colleagues at the A*STAR Institute of Materials Research and Engineering (IMRE) and I evaluate commercially available disinfectant agents available on the market on their effectiveness against viruses. We also debunk common myths about viral inactivation and highlight exciting advances in the development of new sanitizing agents.

No ‘one-size-fits-all’ disinfectant

Depending on the type of surface and ambient conditions, viruses can persist on inanimate surfaces for as short as five minutes to greater than 28 days. A recent study found that SARS‐CoV‐2 can persist longest on propylene plastic surfaces and stainless steel, with viable viruses found up to 72 h after the initial application, though at a greatly reduced viral titer. Much shorter persistence was observed on copper surfaces, with no viable viruses observed after 4 h.

There are many factors to consider when working with disinfection agents. The key parameters that affect their efficacy include contact time, the concentration of disinfection agent and viral characteristics. Disinfection efficacy can also be influenced by environmental factors such as temperature, humidity and pH; the presence of cell debris, soil and aerosolized droplets can also reduce viral penetration and the corresponding activity of the disinfection agent.

Viruses can be classified into three main types—enveloped viruses, large non-enveloped viruses and small non-enveloped viruses—according to increasing difficulty of chemical disinfectant inactivation. Larger viruses are generally more sensitive to disinfectants, although there are exceptions. Non‐enveloped viruses contain a protein coat, and therefore inactivation often requires denaturation of the redundant viral capsid proteins or essential replicative proteins. It is thus challenging to inactivate small non‐enveloped noroviruses and several commonly available disinfectants are not able to sufficiently reduce infectivity.

Commercially available disinfection agents

Alcohols (isopropyl alcohol and ethanol) are capable of inactivating a wide spectrum of bacterial, fungi and viruses, and are ubiquitous in applications such as skin antisepsis and disinfecting small medical tools. While they are effective in eradicating some types of viruses, other types of disinfectants such as surfactants and oxidizing agents are much better disinfection agents compared to alcohols.

Surfactants are particularly useful against enveloped viruses such as coronaviruses, which include SARS‐CoV, MERS and SARS‐CoV‐2. As the active ingredients found in household disinfectants and detergents, surfactants kill viruses mainly by solvating and disrupting the lipid‐based virus envelope. In particular, quaternary ammonium compounds—the most commonly used cationic surfactant—are attractive as they are relatively nontoxic, colorless and odorless.

For noroviruses and other small non‐enveloped viruses that are difficult to disinfect, strong oxidizing agents are among the most effective disinfectants. The most common oxidizing agent disinfectant in the United States is dilute solutions of sodium hypochlorite, also known as household bleach. Other well-known oxidizing agents are hydrogen peroxide and peracetic acid.

Known for its pungent odor, formaldehyde is often sold as an aqueous solution called formalin and used to inactivate viruses for vaccine production. Other aldehydes such as glutaraldehyde and ortho‐phthalaldehyde (OPA) work by the same mechanism, which is to crosslink reactive groups of proteins and nucleic acids. However, not only is formaldehyde a mutagen and suspected carcinogen, it also causes skin and eye irritation.

Debunking myths

While searching for ways to protect ourselves from COVID-19 infection, we must avoid being lulled into a false sense of security by ineffective solutions for which no clear evidence of virucidal properties can be found.

Take for example essential oils, which are topically safe and commonly used in a variety of skincare products to treat dermatological issues such as acne. Despite their popularity, the germicidal abilities of essential oils are mostly bacteria‐related; they cannot be assumed to work on viruses.

Another misunderstood antimicrobial compound is antibiotics. It has been estimated that up to 30 percent of antibiotic prescriptions by medical professionals have been inappropriately used to treat viral infections.

A popular dietary supplement, vitamin C, is frequently recommended in the popular literature for treating respiratory infections, while garlic is known to have fairly broad‐spectrum antimicrobial effects. Another common belief is that rinsing the nose with saline solution, or gargling with salt water, is effective for treating viral infections. However, there is insufficient evidence to prove that any of these dietary supplements or interventions possess virucidal behavior for disinfection purposes.

In contrast, there has been a long history of applying ultraviolet (UV) light in the elimination of microbial pathogens in laboratory and clinical settings. When combating viruses, however, the efficacy of UV disinfection is highly dependent on the absorption by viral DNA and UV dose.

From small molecules to polymers

To expand the repertoire of virucidal compounds available, considerable research effort has been invested in developing new active materials that have both broad spectrum virucidal activity and low toxicity to humans. Although not yet commercially available, three main types of virucidal agents have received significant research attention—small molecules, metal nanomaterials and virucidal polymers.

Small molecules such as β‐cyclodextrins, which are naturally‐occurring macrocyclic molecules comprising of seven covalently‐joined glucopyranose units, are currently being tested for their virucidal properties. Interestingly, some compounds found in food, such as cinnamaldehyde, an organic compound that is responsible for cinnamon’s flavor and odor, have been shown to exhibit virucidal activities.

Metal nanomaterials such as silver and its salts have had a long history of use as antiseptics and disinfectants. Silver nanoparticles between 10 and 100 nm in size are effective biocides in small doses, although their potential toxicities to humans are still under debate. Gold nanoparticles are also promising virucidal agents, but due to the costs involved are unlikely to become commercially viable.

Polymers capable of inactivating viruses are a new and exciting area of research. The vast majority of intrinsically virucidal polymers are charged, and include polyethylenimine (PEI) derivatives, cationic pyridinium‐type polyvinylpyrrolidones and cationic quaternary phosphonium polymers. They can be formulated or cast into various forms for customized applications, such as disinfecting coatings, binders in pharmaceutical products, water purification filters and as additives in paper or common household materials.

Although SARS-CoV-2 is thought to be mainly transmitted by droplets, there is increasing evidence that it might be airborne as well. Airborne transmission of viruses is a major route of human‐to‐human transmission and can occur in the form of aerosols, which are droplets less than five micrometers in diameter. SARS‐CoV‐2 virus particles were found in the ventilation systems of the hospital rooms housing COVID-19 patients in China. Photocatalyst (silver ion‐doped titanium oxide)‐coated air filters and ionizers have recently been demonstrated to be effective in removing viable viruses from the air, although they are not expected to be stand‐alone solutions. Chemical alternatives such as chlorine dioxide are also being studied for inactivating airborne viruses, but more research is needed to understand the long‐term effects of chlorine dioxide exposure.

Balancing biocompatibility and efficacy

In general, disinfectants like aldehydes and oxidizing agents that inactivate viruses by chemically modifying their surface groups are fast‐acting and highly potent towards most viruses, but their application remains limited by their higher toxicity and damaging effects to surfaces.

On the other hand, disinfectants like alcohols and surfactants that mostly rely on dissolving lipid envelopes tend to only show potency towards a narrower range of viruses and may require longer exposure durations, but are often more biocompatible.

The ideal disinfectant agent is one that is effective against a broad range of viruses, acts quickly and is highly potent, but still biocompatible and only mildly damaging to surfaces. Thus, a potential direction may be to develop potent disinfectant agents based on natural compounds that may have less toxicity, which allows the product to be child‐safe and also suitable for long‐term use.

Newer sanitizers with viral inactivation mechanisms that balance broad disinfection efficacy with biocompatibility are thus likely to become the preferred choice for consumers in the future.

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Lin, Q., Lim, J. Y. C., Xue, K., Yew, P. K. M., Owh, C. et al. Sanitizing agents for virus inactivation and disinfection. VIEW. e16 (2020) | article

About the Researcher

Xian Jun Loh

Executive Director

Institute of Materials Research and Engineering
Xian Jun Loh received his PhD in 2009 from the National University of Singapore and joined A*STAR in 2013. A polymer chemist with 20 years of experience working with biomaterials, Loh is currently Executive Director at the Institute of Materials Research and Engineering (IMRE) and Director of Graduate Affairs at the Science and Engineering Research Council (SERC). His research interests lie in the design of supramolecular and stimuli-responsive polymers and hydrogels for biomedical and personal care applications.

This article was made for A*STAR Research by Wildtype Media Group