Israeli scientists at the Israel Institute for Biological Research (IIBR) have found that a combination of two existing antiviral drugs for Gaucher disease appears to inhibit the growth of SARS CoV-2, the virus that leads to COVID-19 and may work against other viral infections, including a common flu strain.
The IIBR is a governmental research center specializing in biology, chemistry and environmental sciences that falls under the jurisdiction of the Prime Minister’s Office. During the pandemic, announcements have been issued by the Defense Ministry.
According to a press announcement on Tuesday, scientists at the secretive bio-defense lab-tested an analog of the FDA-approved drug Cerdelga, and an analog of a second drug, Venglustat, currently in advanced trials. They found that, in combination, the drugs led to a significant reduction in the replication capacity of the coronavirus and to the destruction of the infected cells.
The two drugs are used to treat Gaucher disease, an inherited genetic condition most common in people of Ashkenazi Jewish descent that leads to the buildup of fatty substances in certain organs, particularly the spleen and liver, and can affect their function. The disease can also lead to skeletal abnormalities and blood disorders, In rare cases, Gaucher disease can also lead to brain inflammation, according to the Mayo Clinic. The disease is unrelated to COVID-19.
The Israeli researchers tested the drugs on mouse models using four different RNA viruses: Neuroinvasive Sindbis virus (SVNI), an infection transmitted via mosquitos that can lead to years of debilitating musculoskeletal symptoms; West Nile virus (WNV), also a mosquito-borne disease that can cause neurological disease and is potentially fatal; Influenza A virus, a strain of the flu; and SARS-CoV-2.
The researchers found that the two drugs were effective in all four cases. They work by inhibiting glucosylceramide synthase *GCS), an enzyme involved in the production of glucocerebroside, a lipid that accumulates in the tissues of patients affected with Gaucher disease. In the lab setting, they inhibited the replication of the viruses, and in the case of mice infected with SVNI, increased their survival rate.
In the case of COVID-19, the drugs “have an antiviral effect on the SARS-CoV-2 clinical isolate in vitro, with a single dose able to significantly inhibit viral replication within 24–48 h.”
The two drugs are currently being tested for their effectiveness in treating animals infected with the coronavirus.
The study, published in bioRxiv, has not yet been peer-reviewed. The authors are all from the IIBR’s Department of Infectious Diseases
The data suggests that “GCS inhibitors can potentially serve as a broad-spectrum antiviral therapy and should be further examined in preclinical and clinical trial,” the scientists wrote, adding that repurposing approved drugs can lead “to significantly reduced timelines and required investment in making treatment available.
“Treatment of a new disease such as COVID-19 using an existing, approved drug may serve as an effective short-term solution considering that one of the major challenges in addressing such a pandemic is the length of time it takes for both the research and approval phases of new drugs,” the Defense Ministry wrote in the announcement.