"Unfortunately, if we rely on one channel, the vaccine channel, we may be in a situation where new variants will appear that will hit us on the hip. The variants are a warning sign" says researcher Prof. Shay Arkin
Viral diseases are a serious health threat, as is easy to see through the fight against the corona virus. Furthermore, other viral diseases such as dengue fever, West Nile fever, and Zika fever, exact a significant and painful price especially in the developing world (from the health system to the economy, politics and society). Beyond the prevention of infection through social isolation or wearing masks in the public space, the war against viruses is carried out in three channels - vaccinations, providing antibodies from patients who have recovered, and drug treatment. Even when one of these channels is successful, we should not rest on our laurels since viruses change rapidly and the effectiveness of the treatment of one of the channels (such as vaccines) may deteriorate without prior warning, as can be seen now with the variants of the corona viruses (decrease in effectiveness). Finding cures for 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 the continued struggle against infectious viruses. Two new research papers by Prof. Shay Arkin from the Department of Biological Chemistry at the Hebrew University, published in the scientific magazine Pharmaceuticals, and Viruses focus on finding anti-viral drugs by relying on a particularly weak link that is common in many viruses - ion channels.
What is the ion channel?
Ion channels allow the passage of salts through cell membranes (and internal membranes), and are an extremely important layer in the living world. The viral ion channels allow the virus to regulate the acidity and salinity of its internal and external environment, and are therefore an essential component of the infection pathway. Moreover, ion channels serve as the most common targets in the world of medicine for pharmacological inhibition. Today, substances that inhibit (antagonists) or accelerate (agonists) ion channels are used to treat a large number 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 proven to be effective drug targets.
"As of today, only one type of channel blockers is approved as antiviral agents: the anti-fluo-amino-damantan drugs, which target the M2 protein of influenza, by blocking its channel activity. Unfortunately, widespread resistance on the part of the virus has rendered the amino-adamantans ineffective," the scientific article explains. "Therefore, we decided to look for barriers against the coronavirus in the E protein channel. These barriers may present a potential approach to curbing infectiousness, in particular given the fact that the E protein is the most conserved of all viral proteins. For example, while the spike proteins of SARS-CoV-2 (the current coronavirus) and SARS-CoV-1 (the extinct SARS virus) are only 76.2% identical, their respective E proteins are identical by close to 93.5%. In addition, the channel blockers can serve as a useful research tool for us to clarify the role of protein E in the viral infection cycle."
Don't settle for just vaccines
In the two articles published in leading magazines in the world of virology, Prof. Arkin and his group focused on two channels in the corona virus: the E protein and the 3a protein. In the first study, the researchers scanned a small library of substances approved for human use in order to find inhibitors for this protein, and the results of the scan yielded two inhibitors: gliclazide (a drug used to treat diabetes) and memantine (a drug to treat Alzheimer's disease). In the second and last study, published at the end of last month, a wider material library was scanned (2,839 chemicals from the drug library of MedChem Express) and nearly 10 inhibitors were found. The increase in the amount of inhibitors found increases the chance of finding a cure for Corona. Since all the new inhibitors found are also approved for use in humans, it is expected that all the regulatory hurdles will be less frustrating and less difficult to pass in order to use them for clinical research. "30 percent of the drugs that exist today have been approved in this way, among them of course the drugs that exist today against the corona virus or those that have recently tried to test them against this virus, such as 'remdesivir,'" explains Prof. Arkin and adds: "It must be assumed that the substances found will also inhibit the activity of the corona virus , as experiments recently conducted in the BSL3 laboratory at the Hebrew University in Jerusalem did recently show."
The research is very significant for finding a solution to the variants of the corona themselves. why? The two proteins that Arkin's group focused on are among the most conserved in the virus - the E protein in the current coronavirus is almost completely identical to its counterpart in the SARS virus from 2003 (93.5%), while the spike proteins in the two viruses are only 79.5% identical. Therefore, it can be assumed that all the inhibitors discovered in the latest research regarding the E protein will be relevant to the new variants of the corona virus that break out frequently. Also, while the vaccine works against the component of the virus that changes most frequently, the proteins that Prof. Arkin's research team found to be inhibitory change the least, so there is hope that they will be active against the new variants found in the field, to which the vaccines react less.
The most significant news of the studies done by Prof. Arkin's research team is that pharmaceutical development is progressing and developing in the right directions. "The major barrier that existed - the unavailability of a laboratory to test the materials directly for the corona virus - has been removed. Today we are able to research in a better way and work at a fast pace. Things we thought about a year ago regarding the virus can easily become clear today," Prof. Arkin clarifies, but continues to warn: "The general feeling in Israel and the world is 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 in a situation where new variants will appear that will hit us on the hip. Fortunately, we are not there yet, as far as the market is concerned, but the variants that exist today around the world are a warning light for all of us." The research group hopes to come out soon with another research publication, the third in number, on the effectiveness of the inhibitory substances against the entire virus and not against the E protein alone - a move that may arouse interest among the pharmaceutical companies to start clinical trials on a new drug against the corona virus.
More of the topic in Hayadan:
