COVID-19 Antivirals: New International Study Shows That Carbon-Based Nanomaterials Could Function As Potential Antivirals To Treat COVID-19

COVID-19 Antivirals: A new international research involving scientist from Universidad Católica de Valencia-Spain, Kyoto University-Japan, University of Vienna-Austria, Pingla Thana Mahavidyalaya-India, Indian Statistical Institute-India, University of South Florida-USA, University of Otago-New Zealand, University of Padova-Italy, Yarmouk University-Jordan, CSIR-Indian Institute of Chemical-India, Ulster University-UK, Mayo Clinic-USA, Michigan State University-USA and University of Pittsburgh-USA have in a new study found that Carbon-based nanomaterials could be used as potential antivirals to treat COVID-19.


 
From the study abstract, “Therapeutic options for the highly pathogenic human SARS-CoV-2 causing the current COVID-19 pandemic are urgently needed. COVID-19 is associated with viral pneumonia and acute respiratory distress syndrome causing significant morbidity and mortality. The proposed treatments for COVID-19, such as hydroxychloroquine, remdesivir and lopinavir/ritonavir, have shown little or no effect in the clinic. Additionally, bacterial and fungal pathogens contribute to the SARS-CoV-2 mediated pneumonia disease complex. The antibiotic resistance in pneumonia treatment is increasing at an alarming rate. Therefore, carbon-based nanomaterials (CBNs), such as fullerene, carbon dots, graphene, and their derivatives constitute a promising alternative due to their wide-spectrum antimicrobial activity, biocompatibility, biodegradability and capacity to induce tissue regeneration. Furthermore, the antimicrobial mode of action is mainly physical (e.g. membrane distortion), which is characterized by a low risk of antimicrobial resistance. In this review, we evaluated the literature on the antiviral activity and broad-spectrum antimicrobial properties of CBNs. CBNs had antiviral activity against 12 enveloped positive-sense single-stranded RNA viruses similar to SARS-CoV-2. CBNs with low or no toxicity to the humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria and fungi, including those that are multidrug-resistant.”
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.preprints.org/manuscript/202101.0297/v1
 
The international study team 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 researchers 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.
 
The study team reviewed the evidence available so far on the antiviral activity and broad-spectrum antimicrobial properties of CBNs.
 
The team 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.  
 
Lead researchers Dr Ángel Serrano from the Aroca Biomaterials and Bioengineering Lab, Universidad Católica de Valencia-Spain told Thailand medical News, “CBNs with low or no toxicity t o humans are promising therapeutics against COVID-19 pneumonia complex with other viruses, bacteria, and fungi, including those that are multi-drug-resistant.”
 
While the current 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.
 
So far the novel SARS-CoV-2 virus is the seventh coronavirus known to be capable of infecting humans and the third coronavirus to cause pneumonia.
 
It has been observed that 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.
 
To date there is no effective treatment for COVID-19, with proposed therapies such as remdesivir and hydroxychloroquine demonstrating little or no clinical effect.
 
Dr Serrano added, “Furthermore, antibiotic resistance in bacterial pneumonia treatment is a wide-spread problem.”
 
Currently in the desperate search for alternative COVID-19 treatments, CBNs with intrinsic, broad-spectrum antimicrobial activity are emerging as promising alternatives as COVID-19 antivirals that would likely overcome the issue of microbial resistance owing to the specificity of their antimicrobial mechanisms, say the researchers.
 
The SARS-CoV-2 coronavirus 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.
 
The study team 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.
 
Because CBNs mainly comprise of 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 study team says 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.

Carbon as Fullerene
 
It has been found that 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 research 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. https://pubmed.ncbi.nlm.nih.gov/21666897/
 
Minute Carbon Dots
 
Typically 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.
 
A research in 2016 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929978/
 
https://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra21062g#!divAbstract
 
Another 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). https://pubmed.ncbi.nlm.nih.gov/31633330/
 
Carbon As Graphene
 
The compound 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. https://www.kiche.or.kr/kjche/issue.php?seq=1136656&start=0&number=3&vol=31&num=5&totalcount=25
 
On the whole, the study team found that CBNs had antiviral activity against twelve enveloped positive-sense single-stranded RNA viruses that are similar to SARS-CoV-2.
 
The team says the findings suggest that CBNs are promising alternative antiviral agents against this pathogen.
 
The international study team concluded, “Carbon-based nanomaterials have been evaluated for their antiviral activity against 12 enveloped viruses (HCoV, PRRSV, PEDV, HIV-1, HIV-2, FCoV, JEV, SIV, M-MuLV, ZIKV, DENV, HCV), all single-stranded positive-sense RNA viruses belonging to the same Baltimore group IV as SARS-CoV-2. Most of the studies have shown a potent antiviral activity and from low to no toxicity supporting the potential for the use of CBNs for the treatment of SARS-CoV-2. As a radically novel technology approach for the treatment of COVID-19, these carbon-based therapeutics can provide a significant breakthrough as these nanomaterials allow the targeting of microbial resistance issues and can potentially induce tissue regeneration at the same time. Furthermore, these novel antimicrobial nanoweapons could be employed to deal with SARS-CoV-2 alone or in coexistence with other types of viruses, bacteria, or fungi, causing pneumonia, including multidrug-resistant strains. The chance of success 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. Current methods will provide the means for short-term research, which could already save lives, but more resources will be needed to secure a wider range of research for a larger long-term solution.”
 
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