Can oral medicines fight COVID-19: Weekly Donga


Long ago, there was a dreadful infectious disease called smallpox. It is an acute rash disease caused by the Variola virus, and it is highly contagious because it is a virus that can be spread through coughing or sneezing. At first, I had a headache or suffered from a high fever, but after a few days, flat red spots appeared on my face and limbs. If the spots turned into pus and scabs off, it was cured, but the mortality rate was over 30%. Fads and lulls have been around for a much longer period of time than other diseases. It caused a devastating effect three times more than the Black Death, which killed 300 million people worldwide.

In Korea, from 1910 to more than 50 years, nearly 3,000 cases occurred every year. Even the great leader, Kim Gu, suffered severe smallpox as a child and left traces into adulthood. However, there have been no cases since 1961, and in 1980 the World Health Organization (WHO) officially declared the complete end of smallpox. How did smallpox, a disease that even the royal family dies without measures, have been exalted as ‘mama’, and how did it completely disappear from the world? It is the vaccine that defeats the fear that has driven so many people to lonely and gruesome deaths.

British medical scientist Edward Jenner, called the father of immunology, heard a story about a woman who did not contract smallpox in the village where he worked. She contracted a disease called cowpox from a cow while working as a milker. However, after spontaneous healing without dangerous symptoms, he was not easily infected with smallpox. Jenner was the first to prove that a person who had had vaccinia did not get smallpox over time. As expected, the boy recovered quickly after a slight fever. The word vaccine, derived from the Latin word vaccinus, was born.

At the time, the technology could not know the existence of the virus or the principle of the vaccine, but the method found empirically gave the same results as the current vaccine. Our body activates a defense system called the immune system when external villains such as viruses or bacteria invade. In general, there is an innate immunity that responds once and an acquired immunity that responds by making antibodies according to the characteristics of the villain. Acquired immunity is a bit slow in its initial response, but it has the great advantage of remembering the enemy it has fought once. So, when the virus is moderately weakened and put into the body, the antibodies come out and attack it moderately, then create and share a montage of the downed virus. Now, the villain who visits again with his face sold is recognized as an enemy as soon as he enters, and he is detonated from the antibodies whose memories have been revived and raised a white flag.

Reasons for developing and using vaccines and therapeutics together

A vaccine against COVID-19, which is emerging as the greatest threat to mankind, was developed based on the same principle. However, if the existing vaccines generally inject weakened antigens into the body and generate antibodies through them, there is a slightly different method for the COVID-19 vaccine. This is because the mutation rate of the novel coronavirus is too fast to be used in real viruses, making it difficult to mass-produce it safely and quickly. Instead, the idea was to create something inside the body that could act as a weakened antibody. The new coronavirus has a spike protein that plays a key role in opening the route of infection, and this is what a common cold virus wraps around the body and enters into a fight. It’s called a viral vector, and when some cells infected with it make a spike protein, the immune system builds the corresponding antibody. After that, when a new coronavirus actually arrives, the antibodies that have already remembered the montage will attack it quickly and prevent infection. Alternatively, there is a vaccine that directly delivers messenger RNA (mRNA) corresponding to the blueprint of the spike protein. Seeing the blueprint that enters the body, the cell produces a spike protein, and the immune system watching it also makes an antibody. These attempts make it possible to develop a vaccine safer and faster than the existing methods, but it takes a lot of work to store and distribute.

Vaccination can be said to be an act of sharing a montage before defeating the culprit called a virus. The introduction of the treatment is the process of sending a commando team to successfully break in and catch the rampaging criminal without much damage. There is a term called drug reinvention or recycling. It refers to a method of using drugs that have already passed clinical trials or have proven safety and are on sale for new infectious diseases. Developing a new drug can take as long as 10 years or more because it involves several complex processes. However, the long process is greatly shortened by using an existing drug. It has a lower risk and a higher chance of success compared to an entirely new drug. In short, it is realistic and economical.

Of course, this does not mean that it is easy to prove the efficacy of the developed therapeutic agent. Clinical trials themselves require a lot of time and effort, and there are many pharmaceutical companies whose clinical results do not reach the desired results. However, some of them are judged to have some therapeutic effect. For patients infected with COVID-19, treatment methods vary depending on the severity of symptoms. The important thing is to properly treat patients who are not symptomatic in the early stages after diagnosis so that they do not get worse. Although it can relieve symptoms and suppress damage to the body, there is currently no treatment that can fundamentally eliminate the virus itself. Instead, it blocks or neutralizes the infiltration of the virus into cells as much as possible, helping infected patients to return to their normal routines over time.

Reckonage is an intravenous treatment that is used for a wide range of patients from mild to severe patients. In games and movies featuring unknown infectious diseases, treatments are developed using the blood of the protagonist who has innate immunity. Similarly, reckonage is made from neutralizing antibody genes present in the blood of patients who have been infected with COVID-19 once and have been cured. It is the neutralizing antibody that binds to the virus that enters the body and prevents cell infection. It is now possible to mass-produce neutralizing antibodies obtained by genetic recombination technology. However, since the novel coronavirus mutates so much on the surface, it is vulnerable to response.

Recklonage, remdesivir, and Paxrovide (from left) emerging as COVID-19 treatments. [뉴시스, 사진 제공 · 서울대학교병원, 사진 제공 · 화이자]

Recklonage, remdesivir, and Paxrovide (from left) emerging as COVID-19 treatments. [뉴시스, 사진 제공 · 서울대학교병원, 사진 제공 · 화이자]

Great potential, but concerns

Remdesivir, which is mainly used in severely ill patients, inhibits the replication of the novel coronavirus. It was initially developed as a treatment for clinical trials during the Ebola epidemic, but has been used continuously after it has been confirmed that it is effective against several RNA viruses. The novel coronavirus also needs organic compounds to replicate itself. When remdesivir enters the body, it changes into a form similar to the organic compound required by the virus and competes to prevent replication. Instead of giving them nutritious food, they divert attention and starve to death. Continued research is needed to confirm the efficacy against the mutated virus.

Recently, there is a lot of interest in oral treatments such as paxrovide or molnupiravir, that is, a treatment that is taken in the form of small tablets. Of course, it is because it is much more convenient than going to the hospital and getting an injection. If it is properly established, fears about the underlying dangers of COVID-19 may be diluted to a large extent. Being infected with a virus means that the virus that enters our body transmits genetic information here and there to increase its power. At this time, RNA acts as an intermediate bridge, and it reads and decodes the genetic information written here step by step to make proteins and replicate viruses. At this time, a proteolytic enzyme is required, and Paxrobead is a treatment that blocks this and is effective in the early stage of infection. After the first clinical trial started in March last year, clinical trials are still in progress. According to the interim analysis results, the mortality rate was significantly reduced if the drug was taken within three days of the onset of symptoms.

Molnupiravir sneaks into RNA and causes mutations, which causes problems because the information is not transmitted properly in the process of reading genetic information. it will destroy itself. This method has the effect of inhibiting the replication of many RNA viruses. The U.S. Food and Drug Administration (FDA) Advisory Committee voted for emergency use approval with 13 votes in favor and 10 against. This is a case that reveals that there are strong opinions about how to randomly mutate viruses. A recent study found that molnupiravir reduced the risk of death or hospitalization by half. However, the UK, which introduced molnupiravir for the first time in the world, also approved the conditional approval not to use it for pregnant women, women of childbearing age or lactating women, considering the possibility of affecting DNA replication in human cells. Research on predictable side effects continues.

War should never happen. However, once a war has begun, it is very difficult to find a way to end the war without hurting one ally. It is like the expression of giving flesh and taking bones in the ancient Chinese martial art, ‘Sun-tzu-byeongbeop’. To win the war against the virus, we have already experienced a lot of sacrifice and suffering for a long time. Let’s remember that the secret to being able to manage the H1N1 influenza (swine flu), which was prevalent worldwide in the past, at the same level as the flu, is because the vaccine and treatment were used at the same time. Whether it be a vaccine or a cure, we must do everything we can to win the war that has just begun. And I look forward to seeing how great it would be if we could win all the wars that will happen in the future without giving up flesh or bones based on more advanced science and technology.

Vaccine research to prevent COVID-19, which is emerging as the greatest threat to mankind, continues. [GETTYIMAGES]

Vaccine research to prevent COVID-19, which is emerging as the greatest threat to mankind, continues. [GETTYIMAGES]

The track is… After graduating from the Department of Astronomy and Space at Yonsei University, he worked at the Korea Astronomy and Space Science Institute’s Space Monitoring Center and Yonsei University’s Space Flight Control Lab. Under the stage name of ‘Orbit’, he is running the podcast ‘Changchang’, YouTube’s ‘Unfortunate Science’ and ‘Too Much Science’, and his book is ‘The Science of Orbit’.

Weekly Donga No. 1322 (p60~63)



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