An international team of researchers says that carbon-based nanomaterials (CBNs) could represent promising new approaches to treating coronavirus disease 2019 (COVID-19) pneumonia that is complicated by a secondary bacterial, viral or fungal infection.
The team says that CBNs such as fullerene, carbon dots, graphene, and their derivatives could serve as effective alternatives to currently proposed therapies that have demonstrated little clinical effect or become multi-drug resistant.
Ángel Serrano-Aroca from Valencia Catholic University Saint Vincent Martyr in Spain and colleagues reviewed the evidence available so far on the antiviral activity and broad-spectrum antimicrobial properties of CBNs.
They found that the materials exerted antiviral activity against twelve viruses that are similar to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes COVID-19.
“CBNs with low or no toxicity to humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria, and fungi, including those that are multi-drug-resistant,” writes the team.
An initial version of the review is available on the server Preprints*, while the article undergoes peer review.
COVID-19 pneumonia often complicated by bacterial infection
As COVID-19 continues to sweep the globe posing an unprecedented threat to public health and the worldwide economy, researchers are racing to develop effective therapies to protect against and treat SARS-CoV-2 infections.
The novel SARS-CoV-2 virus is the seventh coronavirus known to be capable of infecting humans and the third coronavirus to cause pneumonia.
In the case of COVID-19, pneumonia is often complicated by infection with Streptococcus pneumoniae, which generally targets the upper respiratory tract and can prove fatal.
Currently, there is no effective treatment for COVID-19, with proposed therapies such as remdesivir and hydroxychloroquine demonstrating little or no clinical effect.
“Furthermore, antibiotic resistance in bacterial pneumonia treatment is a wide-spread problem,” says Serrano-Aroca and the team.
In the urgent search for alternative COVID-19 treatments, CBNs with intrinsic, broad-spectrum antimicrobial activity are emerging as promising alternatives that would likely overcome the issue of microbial resistance owing to the specificity of their antimicrobial mechanisms, say the researchers.
SARS-CoV-2 is an enveloped positive-sense, single-stranded RNA virus. CBNs have previously been shown to exert antiviral activity against these types of viruses in humans, with little or no toxic effects. They have also demonstrated biocidal efficacy against a broad spectrum of bacteria, viruses and fungi, including multidrug-resistant strains.
What did the reviewers evaluate?
Serrano-Aroca and colleagues reviewed a large number of the studies to date that have reported on the broad-spectrum antimicrobial properties and antiviral activity of the CBNs fullerene, carbon dots, and graphene against enveloped positive-sense single-stranded RNA viruses.
Since CBNs mainly comprise carbon, they are biodegradable, biocompatible and can induce tissue regeneration. Furthermore, their successful development as novel antiviral agents is likely, owing to their large surface area allowing interaction with biocompatible polymers that would further enhance their biocompatibility and therapeutic effect.
The researchers say studies have mainly attributed the antimicrobial action of CBNs to physical and chemical mechanisms such as membrane disruption, electron transfer and the induction of oxidative stress by reactive oxygen species. These mechanisms are all characterized by a low risk of antimicrobial resistance.
Main carbon-based structures studied against enveloped positive-sense single stranded RNA viruses.
The high hydrophobicity of pristine fullerene means antiviral fullerene derivatives can be synthesized to produce hydrophilic drugs that readily disperse in water and inhibit viral entry, modify viral functions, and block viral replication.
A study conducted in 2011 showed that C70-fullerene derivatives were highly soluble in water and exerted virucidal activity against HIV and influenza virus. More recently, a new series of fullerene derivatives demonstrated potential inhibition of the hepatitis C virus.
Carbon dots are small CBNs (up to 10 nm in diameter) with a very high surface‐to‐volume ratio that can be homogeneously dispersed in water.
One 2016 study showed that carbon dots could inhibit viral replication of porcine reproductive and respiratory syndrome virus (PRRSV) by activating the interferon response to infection. Another study conducted in the same year demonstrated that carbon dots conjugated with carboxyl phenylboronic acid prevented host cell entry of HIV-1.
A 2019 study of functionalized carbon dots also demonstrated antiviral activity against human coronavirus infections in human liver cells. The dots disrupted viral entry and replication, which was attributed to their interaction with the host cell receptor dipeptidyl peptidase 4 (DPP4).
Graphene possesses excellent physical and biological properties that can be used to detect and destroy viral surface proteins. The high binding affinity of graphene for the essential HIV target proteins (Vpr, Nef, and Gag) was first reported in 2014.
What did the reviewers conclude?
Overall, the researchers found that CBNs had antiviral activity against twelve enveloped positive-sense single-stranded RNA viruses that are similar to SARS-CoV-2.
They say the findings suggest that CBNs are promising alternative antiviral agents against this pathogen.
“The chance of successfully applying these wide-spectrum antimicrobial nanomaterials is very high because of the promising preliminary antiviral results reported for 12 viruses and the fact that the proposed approach could be extended to other types of pneumonia caused by other important pathogens,” concludes the team.
Preprints publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.