Editorial Feature

Analyzing the Antiviral Activity of Graphene Oxide Against COVID-19 and Other Viral Infections

SARS-CoV-2 (COVID-19) is an infectious disease caused by a novel strain of coronavirus. A study published in the journal Current Research in Pharmacology and Drug Discovery has collated the results from research investigating the effects of graphene oxide's antiviral activities. 

Analyzing the Antiviral Activity of Graphene Oxide Against COVID-19 and Other Viral Infections

Image Credit: PopTika/Shutterstock.com

Figure 1 illustrates commonly observed symptoms of the virus, including loss of smell and taste, shortness of breath and cough. The virus penetrates human cells via interaction with the angiotensin-2 converting enzyme (ACE2) in the lungs. 

Graphene oxide (GO), the oxidized form of graphene, is a nanomaterial that can disperse in many solvents. Graphene and GO have a crucial role in the electronic and medical fields as they have been shown to demonstrate antibacterial and antiviral properties.

Symptoms of COVID-19

Figure 1. Symptoms of COVID-19.© Rhazouani, et al., 2021

Furthermore, GO's higher negative charge results in it possessing a high affinity for positively charged viruses; conjugation of GO with antibodies has also been shown to enable quick detection of targeted viruses.

Functionalized graphene shows good viral capture capacity and can be used as a disinfectant. Graphene sensor arrays can be implemented on standard utility textiles and for drug efficacy screening.

This study discusses the mechanism of entry of viruses into host cells and investigates GO's antiviral activity on certain viruses and through photocatalysis. Researchers also analyzed the antiviral effects of the GO-silver complex to fight viruses.

GO and graphene as biosensors for virus detection have also been discussed.

Research

Forging an effective fight against viruses requires in-depth knowledge of how they enter host cells and proliferate to form new viruses. The virus multiplication process involves various steps.

The S protein of the SARS-CoV-2 virus uses the cellular ACE2 receptor to enter the host cell. Figure 2 illustrates how the SARS-CoV-2 virus enters the human cell and proliferates.

Mechanism of SARS-CoV-2 entry into the cell. (1) Spike protein on the virion binds to ACE2. TMPRSS2, an enzyme, helps the virion enter. (2) The virion releases its RNA. (3) Some RNA is translated into proteins by cell machinery. (4) Some of these proteins form a replication complex to make more RNA. (5) Proteins and RNA are assembled into a new virion in the Golgi and 6 Released.

Figure 2. Mechanism of SARS-CoV-2 entry into the cell. (1) Spike protein on the virion binds to ACE2. TMPRSS2, an enzyme, helps the virion enter. (2) The virion releases its RNA. (3) Some RNA is translated into proteins by cell machinery. (4) Some of these proteins form a replication complex to make more RNA. (5) Proteins and RNA are assembled into a new virion in the Golgi and 6 Released.© Rhazouani, et al., 2021

GO exhibits a higher water dispersibility, hydrophilicity, and bonding capacity than graphene. Such physicochemical properties, extremely high mechanical strength, and high surface-to-volume ratio have led to the extensive use of GO as an antibacterial and anti-cancer agent.

Its sharp edges, two-dimensional structure, and negatively charged surface allow it to interact with viruses and break their plasma membrane or produce reactive oxygen species.

GO significantly inhibits infection of PRV, a porcine herpes virus (a DNA virus) that causes Aujesky's disease, and PEDV, a coronavirus (an RNA virus) that infects pigs and leads to dehydration and diarrhea. The strong antiviral activity of GO and rGO can be attributed to the unique monolayer structure and its negative charge.

In vivo and in vitro studies have shown that the hypericin-GO complex (GO/HY) exhibits antiviral activity against New Duck Virus Disease (NDRV), an acute infectious disease of poultry. The GO/HY complex exhibits dose-dependent inhibition of NDRV replication, which can be attributed to the inhibition of virus binding or virus inactivation (see Figure 3).

Description of the main mechanisms of GO’s antiviral activity, (a) including virus inactivation, (b) viral binding inhibition, (c) photodegradation, and (d) electrostatic trapping.

Figure 3. Description of the main mechanisms of GO's antiviral activity, (a) including virus inactivation, (b) viral binding inhibition, (c) photodegradation, and (d) electrostatic trapping. © Rhazouani, et al., 2021

Results

GO has been established as an excellent nanomaterial for high-throughput detection and disinfection of viruses, as well as great potential to inhibit environmental infections. Meanwhile, curcumin-functionalized GO acts effectively to inhibit infections caused by the respiratory syncytial virus (RSV).

Curcumin-functionalized GO was also found to be highly biocompatible with host cells, indicating a new pathway of antiviral therapy for RSV infection (see Table 1).

Table 1. The antiviral activity of GO. Source: Rhazouani, et al., 2021

Virus  Family Species Nucleic
acid
Viral
envelope
GO Ref
RSV Pneumoviridae  Human
orthopneumovirus
RNA enveloped GO Yang et al.
(2017)
VSV Rhabdoviridae  Indiana
vesicolorum
RNA enveloped GO Gholamiet
 al. (2017)
H9N2 Orthomyxoviride  Influenza A RNA enveloped GO Songet al.
(2015)
IBDV Birnaviridae  Infectious Bursal
disease virus
RNA Non-
enveloped
GO-AgNPs Chen et al.
(2016)
NDRV  Reoviridae  – RNA Non-
enveloped
GO/HY D. Xet al.
(2019)
FCoV Coronaviridae  Alphacoronavirus 1 RNA enveloped GO-AgNPs Chen et al.
(2016)
PEDV Coronaviridae  Porcine epidemic
diarrhea virus
RNA enveloped GO Yeet al.
(2015)

 

Nanocomposites with GO and partially reduced sulfonated GO suppressed infections by herpes simplex virus type 1 (HSV-1) by inhibiting the virus from binding to host cells. GO also exhibits superior photocatalytic activity that can be leveraged to suppress virus activity. The virus must stay close to the GO surface under UV irradiation (see Figure 3).

When compared to graphene, GO exhibits a higher bactericidal activity as its concentration considerably affects bacterial viability. At lower concentrations, GO forms floating scaffolds that promote bacterial growth. However, at higher concentrations, it forms scaffolds that can inhibit bacterial growth.

The combination of AgNPs with antiviral activity and GO with antimicrobial potential has exhibited antiviral activity against both non-enveloped and enveloped viruses.

Viral inhibition tests employed to determine the antiviral activity of the GO-AgNPs complex demonstrated that this complex suppressed 25% of feline coronavirus (FCoV) infection, while inhibiting 23% of IBDV infection. By contrast, GO alone was found to inhibit only 16% of FCoV infection, while showing no antiviral activity against IBDV infection.

SARS-CoV-2 infection has been detected using two main methods:  the first utilizes CRISPR, while the second is based on the identification of antibodies specific to viral antigens. Studies have shown that nanosensors are regarded as the most potent way to detect the novel SARS-CoV-2.

Researchers have been able to make a new class of biosensors thanks to the evolution of various carbon-based nanomaterials, like graphene, GO, and carbon nanotubes.

Graphene is specifically regarded as a key element for making biosensors. Besides finding use as graphene-based sensors to detect human diseases, they have also been applied in the areas of agriculture, food, and aquaculture to fight specific viruses.

GO nanosheets exhibit excellent physicochemical and biological properties, and are thus used to make protective equipment against infectious diseases. These properties may provide new benefits for regulating SARS-CoV-2 and minimizing its spread.

A multifunctional cotton fabric with ultra-strong UV protective properties and high electrical conductivity has been made by applying a dispersion of GO's nanosheets to the fabric's surface through the vacuum filtration deposition method.

Figure 4 illustrates the potential multifunction of GO that may prove helpful against the virus at different levels. Thus, GO could be employed as a biosensor to detect viruses and manufacture protective equipment against infectious diseases because of its mechanical properties.

Representative uses of GO to combat viruses.

Figure 4. Representative uses of GO to combat viruses. © Rhazouani, et al., 2021

Conclusion

GO-based nanomaterials are potential candidates to tackle different types of viral infections, such as COVID-19.

GO and graphene can inactivate different viruses by various mechanisms, and have been demonstrated to be highly useful for high-throughput diagnostics that involve using a transistor-based biosensor that can detect SARS-CoV-2. Their inclusion in protective equipment against infectious disease is an area of research sure to develop. 

Further research is essential to design new GO-based antivirals to combat SARS-CoV-2 and other viral agents. In particular, more insights must be gained into the toxicological mechanisms of nanomaterials to improve their integration into the biomedical field.

Continue reading: Effect of Nano-Perovskite Structure on Suppressing the SARS-CoV-2 Infection.

Journal Reference:

Rhazouani, A., Aziz, K., Gamrani, H., Gebrati, L., Uddin, M. S., Faissal, A. (2021) Can the application of graphene oxide contribute to the fight against COVID-19? Antiviral activity, diagnosis and prevention. Current Research in Pharmacology and Drug Discovery, 2, p. 100062. Available online: https://www.sciencedirect.com/science/article/pii/S2590257121000493?via%3Dihub.

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Megan Craig

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Megan Craig

Megan graduated from The University of Manchester with a B.Sc. in Genetics, and decided to pursue an M.Sc. in Science and Health Communication due to her passion for combining science with content creation. As part of her studies, Megan partnered with Jodrell Bank Discovery Centre as a Digital Marketing Assistant, producing content and updating sections of their website. In her spare time, she loves to travel, exploring each location's culture and history - including the local cuisine. Her other interests include embroidery, reading fiction, and practicing her Japanese language skills.

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    Craig, Megan. 2022. Analyzing the Antiviral Activity of Graphene Oxide Against COVID-19 and Other Viral Infections. AZoNano, viewed 17 May 2022, https://www.azonano.com/article.aspx?ArticleID=5918.

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