With the urgent need for COVID-19 treatment and the lack of drugs with known efficacy, doctors and scientists have used a proven strategy since the outset of the pandemic, trying to use existing, safety-validated and approved drugs for other diseases.
One candidate was amantadine, which was used to treat influenza in the last century. Initially effective in relieving symptoms caused by type A virus, it has failed relative to influenza B virus. Over time, influenza viruses have become resistant to its effects and is now used primarily in patients with Parkinson’s disease (as a tremor-reducing drug). It is available as amantadine sulfate and hydrochloride.
Two new SARS-CoV-2 viroporins have been identified
During the COVID-19 pandemic, there were suggestions that the effects of amantadine could be used to prevent infection caused by the SARS-CoV-2 coronavirus and to alleviate the course of the disease.
In an article just published in (belonging to the “Nature” group) journal “Communications Biology” Scientists from Denmark, Germany and Greece have shown that amantadine and hexamethylene amiloride (HMA) block the activity of the E protein ion channel from SARS-CoV-2 virus – viroporin found in the envelope of coronaviruses. However, the amantadine derivative rimantadine does not have such an effect.
Viroporins are small proteins encoded by viruses that create pores in the host cell’s membrane. This activity modifies several cellular functions, including membrane permeability, calcium ion balance, membrane remodeling, and glycoprotein transport. Protein E is a viroporin present in the envelope of the SARS-CoV-2 virus.
Amantadine and HMA bind to protein E as assessed by solution NMR simulation and molecular dynamics. By the way, the authors identified two new SARS-CoV-2 viroporins: ORF7b and ORF10, showing the activity of the ion channel in the expression system of the frog’s oocytes (Xenopus laevis). Amantadine also blocks the activity of the newly discovered ORF10 ion channel, which means it could potentially act for two purposes in COVID-19 patients.
“Amantadine: a new, cheap and effective treatment for COVID-19”
“That is why we are proposing amantadine as a new, cheap, readily available and effective treatment for COVID-19,” write the authors of the study.
The article was sent to the magazine in December last year, but it has only been published now. Previous work has already informed about the ability of amantadine to block ion channels. As countless cases of potential drugs for cancer and other diseases have shown, the effects observed in laboratory conditions do not mean that the drug will work in a sick person, experts note.
In Poland, clinical trials on the use of amantadine in the treatment of COVID-19 began in April 2021. Two projects received nearly PLN 15 million in funding from the Medical Research Agency and are coordinated by centers in Lublin and Silesia. Scientists from the Medical University of Silesia in Katowice have undertaken to verify the effectiveness of amantadine treatment in patients with COVID-19. 500 patients were expected to participate in the clinical trial. In turn, the team from the Department of Neurology of the Independent Public Clinical Hospital No. 4 in Lublin was part of an international consortium conducting research on the effectiveness of amantadine and its derivatives in the treatment of SARS-CoV-2 infections. This research is still ongoing.
Experts so far do not recommend taking amantadine for COVID-19.
heat / PAP