Oct 18, 2021
JERUSALEM WEATHER

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Researchers and pharmaceutical companies around the world are searching desperately for new or existing drugs than can help overcome the COVID-19 virus. Now, the Hebrew University of Jerusalem (HUJI) has reported that there are three existing drugs that fight the new coronavirus with “almost 100%” success in human cells in in-vitro (lab) tests.  

Viral diseases pose a serious health threat, as can be easily seen regarding the fight against the coronavirus. Other viral diseases such as dengue fever and West Nile fever carry a significant and particularly painful price in the developing world. Beyond preventing infection through social isolation or wearing masks in public space, fighting viruses is done in three channels – vaccinations, administration of antibodies from patients who have recovered and drug treatment. 

Even when one of these channels is successful, viruses change rapidly, causing reduced effectiveness of the new vaccines against the coronavirus variants. Finding drugs against the diseases, therefore, is not a matter to be taken lightly, and the many research works currently being done in the field are critical to continuing to deal with the contagious viruses. 

Two new research papers by Prof. Shai Arkin of the department of biological chemistry at the Hebrew University of Jerusalem (HUJI), have been published in the scientific journal Pharmaceuticals under the title “Identification of SARS-CoV-2 E Channel Blockers from a Repurposed Drug Library.” They focus on finding antiviral drugs based on a particularly weak link in many viruses ion channels. Arkin and his team looked for antiviral drugs that exploit a weak link in many viruses – proteins called ion channels.

Ion channels enable the virus to regulate the acidity and salinity of its internal and external environment. Blocking those channels makes it difficult for infections to spread. So far, only one ion channel blocker is approved as an antiviral treatment, and that is for the flu.

These allow the passage of salts through cell membranes and are very important in the animal kingdom. Viral ion channels allow the virus to regulate the acidity and salinity (saltiness) of its internal and external environment, and they therefore constitute an essential component in the pathway of infection. In addition, ion channels are used as the most common targets in the medical world for drug inhibition. 

Until now, the envelope protein was not seen as a promising target for drugs. But Arkin’s group identified it as an ion channel protein located in the membranes of all organisms that, because of their structure, respond particularly well to drugs, a quality exploited by pharmaceutical products for chest pains, hypertension and many other conditions.

Arkin explained that the envelope protein in the SARS-CoV-2 virus is about 95% identical to that of the first SARS outbreak of 2003, but the spike protein is less than 80% identical.

Today, inhibitors (antagonists) or catalysts (agonists) ion channels are used to treat a wide range of diseases such as degenerative diseases, cystic fibrosis, cystic fibrosis, epilepsy, epilepsy, heart rhythm disorders, hypertension and more. It is important to note that ion channels in viruses have been shown to be effective drug targets.

Currently only one type of ion-channel blocker is approved as an antiviral substance: the anti-fluo-amino-diamant drug, which targets the M2 protein of influenza, by blocking its channel activity. Unfortunately, widespread resistance on the part of the virus has made it less promising. 

The most significant news emanating from Arkin’s research team is that drug development is advancing and evolving in the right directions. “The big barrier of the unavailability of a lab to test the substances directly on the coronavirus has been eliminated. Today we are able to research better and work at a fast pace. Things we thought about a year ago about the virus can now be easily clarified,” Arkin declared. 

The general feeling in Israel and around the world was that if there are vaccines, there is no reason to continue working on the virus because we have found a solution. Unfortunately, if we rely on one channel, the vaccine channel, we may be stuck. As the mRNA vaccines against the virus have proved to offer excellent protection but that this falls below 95% over time, especially against the Delta variant, the use of supplementary medications would be very useful. Almost a third of all medications drugs available today have been approved in this way, including the drugs currently available against the coronavirus or those recently tested against this virus, Arkin noted. 

If the medications are found effective in patients, they will probably be useful in overcoming the new, more infections variants, as they target proteins that hardly change between mutations. He and his team scanned 2,839 substances and found the three drugs that were impressive candidates.

When they mixed the medications with live SARS-CoV-2 and the human cells, they found that almost all of the cells survived even though they had been infected by the virus. This compares with what usually happens, in which about 50% of the cells would have died a couple of days after they were in contact with SARS-CoV-2. 

If an existing drug is effective, it greatly shortens the time needed to get approval, as it has already been okayed by the US Food and Drug Administration, Israel’s Health Ministry, and other regulatory agencies. 

The three medications are cancer drug Flumatinib (an orally bioavailable tyrosine kinase inhibitor); darapladib (an inhibitor lipoprotein-associated phospholipase A2 developed for the treatment of atherosclerosis); and an HIV medicine. 

Although much work, including clinical trials and regulatory agency approval, must be done to prove efficacy, Arkin concluded that he was enthusiastic about the possibility of helping to widen the weapons science has against the coronavirus. 

 

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