BREAKING! Spanish Scientists Claim That Cheap Natural Cyclodextrins Especially Beta Cyclodextrins Can Be Used As Antivirals Against SARS-CoV-2!
: A new study by researchers from Spain led by scientist from the Cell Structure Lab, Centro Nacional de Biotecnologia, CNB - CSIC, Campus de Cantoblanco, Madrid -Spain has found that cheap natural cyclodextrins especially Beta Cyclodextrins can be used as antivirals against SARS-CoV-2!
Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzymatic conversion. They are used in food, pharmaceutical, drug delivery, and chemical industries, as well as agriculture and environmental engineering. They are very easily available, extremely cheap and have a non-toxic profile.
The current ongoing COVID-19 pandemic is facing new surges globally with a variety of newly emerging Omicron variants and sub-lineages alongside the debut of numerous recombinant variants.
To date, there are no real antivirals that can be really used to treat or prevent COVID-19 infections and all the so-called U.S. FDA drugs like remdesivir, paxlovid, molnupiravir etc are all simply hype and controversial. There is an urgent need to discover or develop newer safer and effective antivirals to deal with the SARS-CoV-2 variants and sub-lineages.
The study team aimed to identify a cost-effective antiviral with broad spectrum activity and high safety and tolerability profiles.
The researchers began analyzing a list of 116 drugs previously used to treat other pathologies or characterized in pre-clinical studies with potential to treat coronavirus infections.
They next employed molecular modelling tools to rank the 44 most promising inhibitors and tested their efficacy as antivirals against a panel of alpha and beta coronavirus, e.g., the HCoV-229E and SARS-CoV-2 viruses.
Interestingly, four drugs, OSW-1, U18666A, hydroxypropyl-beta-cyclodextrin (HbetaCD) and phytol, showed antiviral activity against both HCoV-229E (in MRC5 cells) and SARS-CoV-2 (in Vero E6 cells).
The detailed mechanism of action of these compounds was studied by transmission electron microscopy (TEM) and by testing their capacity to inhibit the entry of SARS-CoV-2 pseudoviruses in ACE2-expressing HEK-293T cells. The entry was inhibited by HbetaCD and U18666A, yet only HbetaCD could inhibit SARS-CoV-2 replication in the pulmonary cells Calu-3.
Considering these initial findings and given that cyclodextrins are widely used for drug encapsulation and can be safely administered to humans, the study team further tested 6 native and modified cyclodextrins, which confirmed β-cyclodextrins as the most potent inhibitors of SARS-CoV-2 replication in Calu-3 cells.
All accumulated data points to beta-cyclodextrins as promising candidates to be used in the therapeutic treatments for SARS-CoV-2 and possibly other respiratory viruses.
The study findings were published on a preprint server and are currently being peer reviewed.
A previous study in 2021 had also showed that cyclodextrins could be used an antiviral against the SARS-CoV-2 virus.
A Brazil study also showed that Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines.
French based food and biotech company had also produced a white paper detailing the usage of cyclodextrin to treat COVID-19.
Numerous past studies had also showed that cyclodextrins can be used as antivirals against a wide range of viruses including HSV. RSV, Dengue, Zika, HIV, various coronaviruses etc and in fact they demonstrated broad-spectrum antiviral activity.
In fact, a number of studies and even small clinical trials were conducted involving cyclodextrins against SARS-CoV-2 but strangely no COVID-19 News
outlets covered these studies and trials.
According to the Spanish study team, though pathogenic viruses pose a real and growing threat to public health, they are still a few medicines and drugs available to prevent and treat viral infections.
The study team created a library of potential inhibitors of coronavirus infection that was further elaborated with a “based-on-knowledge” strategy. By examining the available information about what viruses use to complete their life cycle in cells and the description of the mechanism of action of drugs, the study team found compounds with potential to be used as antivirals to treat coronavirus infections. The main advantage of this strategy compared to high-throughput analysis is that the list of candidates is limited, and that different protocols of infection and drug treatment can be tested, which increases the probabilities of identifying molecules with antiviral activity.
The study team used a unique workflow involving biocomputational analysis and several biological assays to carefully select potential antivirals against different coronaviruses, including HCoV-229E and SARS-CoV-2.
From a list of 116 compounds that target cell factors and pathways, 4 showed antiviral activity against both coronaviruses.
Importantly, results with β-CDs were particularly relevant as showed consistent efficacy in different cellular models including human pulmonary cells.
Particularly promising is the finding suggesting that the mechanism of action of β-CDs is interfering with viral fusion. Results from lipidomic analysis and transmission electron microscopy (TEM) showed that βCDs may interfere with coronavirus infection by altering cholesterol and sphingomyelin content and disrupting the organization of membranes used by the virus.
The study findings are supported by the study team’s TEM results that showed dose-dependent effects of β-CDs in all SARS-CoV-2 structures in infected cells. The integrity of DMVs was compromised and viral morphogenesis was impaired, with the production of abnormal viral particles that are sometimes trapped in DMVs (Double-membrane vesicles) and inside large vacuoles that could represent degradation compartments.
The study findings confirm and broaden past study findings that focused on HP-β-CDs and with different methods further expand these results to other members of the cyclodextrin family and to SARS-CoV2 VOCs, including Omicron variants and sub-lineages.
Considering that cyclodextrins can be suited for oral, nasal or nebulized solutions, these results open different avenues to test diverse drug formulations that are known to be safe in humans.
Future detailed research should address the potential activity of these compounds in ameliorating SARS-CoV-2 infection in relevant animal models. The well-known safety profiles of β-CDs render these molecules as ideal candidates to develop affordable prophylactic and therapeutic compounds against coronaviruses.
In fact, such drugs, which are already approved for clinical use in nasal spray devices, may be easier to deploy in low-income countries compared to vaccines, which often require cold storage and must be administered by trained personnel.
Also considering the fact that β-CDs are already widely used for compound encapsulation, they could be easily combined with other antivirals to potentiate activity and avoid viral resistance.
Significantly, the wide mechanism of action shown herein, which inhibits viral fusion with cellular membranes, could help to counteract other respiratory viruses, providing an arsenal to deploy in front of new variants of concern or future novel coronaviruses with pandemic potential. Broad-spectrum antivirals such as β-CDs could be ultimately applied to counteract unknown emergent viruses yet to appear, but need rigorous assessment in preclinical models for further development.
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