β-cyclodextrins prevent SARS-CoV-2 and HCoV-229E infection in cell cultures, primary tissues and animal model
The pandemic caused by SARS-CoV-2 has highlighted the lack of drugs against coronaviruses, a family of viruses that cause various conditions, from the common cold to severe respiratory diseases. Now, a study, co-led by IrsiCaixa and the Centro Nacional de Biotecnología CNB-CSIC, together with the Universidad Católica San Antonio de Murcia, reveals the potential of β-cyclodextrins as a preventive drug against SARS-CoV-2 and HCoV-229E, viruses representing two of the four genera of the coronavirus family. Specifically, the team shows the potential of this drug, chosen from 116 compounds studied, because it has proven to be able to prevent infection in cell cultures, primary tissues and animal model. Having an affordable and safe drug such as β-cyclodextrins would allow prevention strategies against the current SARS-CoV-2 pandemic or against possible outbreaks of other coronaviruses, as well as future coronaviruses that may emerge.
Although vaccines have been a key tool in controlling the SARS-CoV-2 pandemic, they do not reach low-income countries and may be ineffective for people with compromised immune systems who are vulnerable to severe infection. "We want to offer a preventive option to this group that is currently not protected, but we are going even further, since we are looking for drugs that are broad-spectrum, that is, that not only allow us to prevent infection by SARS-CoV-2 but also by other subtypes of the coronavirus," explains Nuria Izquierdo-Useros, principal investigator at IrsiCaixa.
The search for an affordable, effective and broad-spectrum drug against coronaviruses
The team started the study with a list of 116 existing and approved drugs that, based on their characteristics, were potential candidates for inhibiting coronavirus infection. Using a computational study based on molecular modelling, the researchers selected the 44 most promising drugs, which were used for computational chemistry, virology, cell biology and electron microscopy studies. All these data led to the identification of four compounds with the potential to block infection by SARS-CoV-2 and HCoV-229E, two viruses belonging to the β and α coronavirus genera, respectively. Of all the compounds they tested, β-cyclodextrins were the best at inhibiting infection. Specifically, β-cyclodextrins are able to prevent SARS-CoV-2 and HCoV-229E infection in cell culture and in models simulating human nasal epithelium in the laboratory. Moreover, when administered intranasally in animal models, they do not become infected, or become infected with a lower viral load, when they come into contact with SARS-CoV-2.
"The evidence of its preventive function against SARS-CoV-2 infection is clear and, considering that we are talking about an affordable and highly safe drug, the results support the initiation of clinical studies to evaluate the usefulness of this drug as a prophylactic antiviral against COVID-19," concludes Dàlia Raïch-Regué, senior researcher at IrsiCaixa.