Pictured: An artificial synthetic protein (red) is combined with coronavirus instead of human cells to block infection
(Source= University of British Columbia, Canada)

[메디게이트뉴스 배진건 칼럼니스트] After the nightmare SARS-CoV in 2002, researchers studied how SARS infiltrated humans. Corona viruses, as their name suggests, are important weapons for intrusion into humans by spiked proteins protruding like crowns on the outside. It has been reported that ace2, a cousin of angiotensin-converting enzyme (ACE), the receptor for the corona virus that causes sars. SARS-CoV-2, the brother of nightmare sars throughout the world, is now known to invade our bodies using the same receptor ACE2.

In an easy-to-understand picture, a receptor protein called ACE2, our body’s lock, opens the door to human cells with the key to the spike protein of the corona virus. The more the key spikes bind well to the lock ACE2, the more the human body intrusion pathway opens, causing the infection to occur well.

Ace is known before ACE2, which acts as a pathway to this corona virus intrusion. ACE lenin to control the blood pressure of our body – an important enzyme of the angiotensin system and acts on angiotensin and bradykinnin to constrict blood vessels and result in high blood pressure. Therefore, ACE inhibitors are effective in the treatment of hypertension and congestive heart failure.

ACE2 has a similarity of 42% of the metalloprotease catalytic domain of ACE, angiotensin II (Ang II) angiotensin 1-7[Ang-(1-7)]In addition to switching to the ACE and physiological or pathological changes are involved in the generation of AngII and Ang- (1-7). However, ACE and ACE2 is protease (protease) decomposes the peptide in different locations and has different substrate specificities.

The co-founding team of Professor Yosef Penninger of the University of British Columbia, Canada, Sweden, Spain, and Austria, published a paper in the international journal Cell on April 2 entitled ‘Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2’. This paper opens up clinical possibilities by demonstrating in cell experiments that human proteins combined with corona viruses can be artificially synthesized to combat the virus.

The researchers were the first to confirm that the same ACE2 protein was a pathway to the virus’s penetration, even when SARS-CoV was in the gut. This time, sars-CoV-2 is also a team that first published the results of the study using ace2 receptors to invade our body.

What’s more, the protein ACE2 in our body has the ability to prevent lung damage, using ace2 knock out mice to prove why SARS is called the disease of severe acute respiratory syndrome genetically. He predicted that if the key spike protein prevents it from binding to the lock ACE2, it could be a therapeutic agent for Corona 19 (COVID-19).

ACE2 is a protein having an activity by being cut from the cell surface to the cell membrane protein. Ace2 protein, a form of soluble in water, is also referred to as ‘Decoy ACE2’ because it is a protein that removes the original cell membrane portion. The researchers synthesized the so-called human recombinant soluble ACE2 (hrsACE2) into a gene that makes ace2 proteins.

Let’s inject the hrsACE2 protein used in the current clinical vero E6 kidney cells (kidney cell) infected with corona virus surprisingly the virus was plunged to 1/1000 to 5000. However, injecting a protein made of mouse rsACE2 gene in mice into the control group had no effect on the virus. The researchers explain that corona viruses can’t be replicated by combining hrsACE2 proteins into cells by mistakenly combining them into a pathway that invades cells.

In this experiment, the researchers experimentally showed that the organoids and kidney organoids, a mini-organ made from human stem cells, are infected with the virus. In addition, when injected with hrsACE2 protein before the artificial organs are infected with the virus confirmed the effect of virus eradication that the virus does not accumulate in the organoids. These experimental results predict that the same phenomenon will occur in organs in our bodies.

The importance of this study is that the corona virus has proven to be treatable when combined with the water-soluble ACE2 protein instead of ACE2 present in the host cell. The war of humans and viruses is clever with each other. Ace2 protein, which acts as a preventing lung damage in our body, is to be used as an intrusion pathway into the lungs by the corona virus. Human beings are a strategy to prevent the intrusion of viruses by injecting the keys of the virus in large quantities with can locks. Who will win the war?

Photograph: Apeyron Bylogic’s website

Aperion bylogics (APERION Biololgics) located in Vienna, Austria, the hrsACE2 is named ‘APN01’ and is currently undergoing clinical phase 2 for acute lung damage (Acute Lung Injury, ALI) / Acute respiratory distress syndrome (Acute respiratory distress syndrome, ARDS) and pulmonary arterial hypertension (Pulmonary arterial hypertension, PAH). Therefore, hrsACE2, an artificial protein used in this corona virus penetration prevention experiment, is already the highest-grade protein used in clinical trials.

ARDS is a disease that is difficult to breathe suddenly due to lung inflammation caused by infection without heart problems in clinical. In ARDS, due to a variety of causes, the permeability of the alveoli capillary membrane is increased and the liquid is leaked into the alveoli space, hypoxia and inflammatory acute pulmonary damage occurs.

According to the case study, a 3-year-old man had a fever seven days earlier and had difficulty sleeping at night because he had a fever three days in the air. There were no specific findings in the chest photo taken the day before the hospitalization, but the child was struggling to breathe on the day of the hospitalization. In auscheongjin, a wheezing and pneumonia sound was heard throughout both lungs. These symptoms are similar to symptoms caused by corona virus.

One-third of U.S. adults have high levels of hypertension. PAH, on the other hand, is a rare disease that is estimated to have taken 50 to 100 people per million people. PAH is a form of hypertension that occurs in the lungs and may occur due to a variety of factors, such as apnea and chronic obstructive pulmonary disease (or generally COPD) during sleep.

PAH is one of the types of pulmonary hypertension that narrows and tightens the blood vessel walls of the arteries leading from the right side of the heart to the lungs. As a result, increased pressure in the lungs leads to symptoms such as fatigue and shortness of breath. PAH deteriorates over time and there is a high demand for unmet treatment to date.

Professor Joseph Fanninger, the lead author of this cell paper, has been focusing on ACE2 proteins since 2000. He co-founded Aperion Bylogic in 2003 in order to develop new drugs that save people from his research. The failure of ace2 proteins is a factor in diseases such as ALI / ARDS and PAH, so we are conducting clinical phase 2 at the end of research and development with the goal of treating these sufferers.

For a long-time preparing person, chances come. The hrsACE2 protein in the ‘APN01’ code has already been clinically underway in Europe, so it has enough information about safety and capacity. Thus, first demonstrated in cell experiments that can fight the virus by artificially synthesizing the human protein ACE2, which binds with SARS-CoV-2, aperitif by logic was able to immediately start clinical phase 2 in Austria, Germany, Denmark as a corona 19 therapeutic agent.

The Republic of Korea should invest in a group of researchers who are constantly researching and preparing for the virus that will come back one day. “Chance favors only the prepared mind,” Dr. Pasteur said, “and it really touches me when I get hit by sars-CoV-2. Like the five wise virgins who prepared torches and oil to greet the bridegroom, preparation is prepared. How do you prepare for an uncertain future? We have no choice but to stick to the present. Being faithful to the present prepares for the future.

*The column is a columnist’s personal opinion and may not match the editorial direction of Medigate News.



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