[쿠키뉴스] Reporter Han Sung-joo : Academia and the pharmaceutical biotechnology industry around the world are focusing on the development of corona 19 drugs. As a drug to combat the new virus, antiviral agents of various mechanisms have been utilized in clinical trials. Experts from global companies and research institutes gathered at BioKorea 2020 to introduce the development of corona 19 therapeutics.
Currently, most of the drugs that have started clinical trials as corona 19 therapeutic agents are cases of “drug re-creation”. Drug re-creation is a new drug development method to determine whether the drug that was initially developed for the treatment of other diseases has therapeutic effect and safety for new diseases. Lee, ceo of BridgeBiotherapeutics, described three types of viral drugs. Substances being developed as corona 19 therapeutic agents ▲ mechanisms that act directly on the virus (Direct Antivirals) ▲ immune force to prevent the virus by enhancing the mechanism (Immune Boosters) ▲ anti-inflammatory (Anti-inflammatory) to reduce inflammation after symptomexpression is typical.
Photo: Gilliard Science homepage
Corona 19 therapeutic candidate directly acting on the virus is representative of “Lemdesivir”. Research to determine the effect of corona 19 treatment of this drug is actively being conducted worldwide. However, Lee said, “Conflicting results on the validity of the results have been repeatedly announced, making it difficult to determine the possibility of corona 19 as a treatment.”
A typical candidate for a mechanism to increase immunity is interferon alpha. This is a kind of cytokines that the human body secretes to combat the intrusion of viruses into proteins present in the human body. Bevacizumab, which is used as an anti-cancer drug, is also being conducted in clinical trials for corona 19 patients. Immuno-anticancer components such as ‘nivolumab’ (product name: Opdivo) and ‘pembrolizumab’ (product name: Kitruda) are also mentioned as candidates for corona 19 therapeutics. These drugs are the principle that kills the cells infected with the virus and enhances the ability of the human body to cope with the virus.
Since corona 19 symptoms are expressed as a mechanism for inhibiting the progression of inflammation has attracted attention antibody drugs called “adalimumap”. “Bari city nip”, “rock sori tinip”, “topa city nip” etc. inhibiting the jack (JAK) protein present in inflammatory cytokine cells are also in the clinical trial for corona 19 patients. A clinical trial for the cytokine antibody drug “IL-6” and rheumatoid arthritis drug “tosilizumab” (product name: Actemra) is also underway.
In addition, drugs of the mechanism (Anti-spike proteins) binding to the spike protein of the virus is also urgently developed. It is a principle that prevents the receptors of the virus surface from sticking to the cells of the human body to inhibit viral infection. However, these types of candidates are most likely not yet entered clinical trials. Multinational pharmaceutical and biotechnology companies such as Bioterra Solutions, Clio Pharmatherapeutics, Bir Biotechnology and GSK, Bribio, Regeneron Pharmatherapeutics, and Celltrion, among domestic companies, have also challenged the development of the drug.
When will it be time to meet the commercialized Corona19 remedy, not a candidate? Dr. Kim Mi-hyun of the Korea Chemical Research Institute said, “There is a situation where substances specialized in the treatment of Corona 19 have not been developed,” and he advised, “Typically, new drug development takes 10-15 years, so we need to think about strategy in the long run.” By the way, there are 452 clinical trials of corona 19 worldwide as of the end of last month. The most clinical trials were conducted in the drug is ‘hydroxychloroquine’, ‘lopinavir / ritonavir’ (product name: calletra) and ‘tosilizumab’ followed by the number of clinical trials started.
Dr. Kim added, “Considering the nature of RNA viruses that cause mutations easily, we need to develop antiviral drugs with a broad spectrum.” That is, it is necessary to have a drug having an effect on a variety of corona viruses, as well as corona 19. The immediate urgent task was to establish an animal testing model, to establish large-scale production facilities, and to create a joint research environment for governments, academia, and corporations.
Various attempts have been made in Korea. The Korea Pasteur Research Institute selected 24 drugs as a candidate for corona 19 therapeutics. Research is also underway to change the formulation of the insect repellent component to reborn as a corona 19 treatment.
Dr. Kim Seung-taek of the Institute received sascoronavirus-2 from the Centers for Disease Control on February 17 for drug re-creation. Over the next three weeks, 48 drugs were selected as candidates for the development and optimization of virus-specific methods. Among them, 24 drugs were re-selected through efficacy analysis, the virus concentration reaction analysis confirmed that “siklesonide” had a strong virus suppression and low cytotoxicity.
Siklesonaid is a drug developed for the treatment of asthma. The institute estimates that the drug may also play a role in inhibiting viral activation and reducing inflammation as a steroid-based drug. Currently, a researcher-led clinical trial of Ciclesonaid is underway for 141 patients with Corona 19.
The institute also confirmed the low cytotoxicity and vigorous antiviral effects in the insect repellent component “niclosamide”. However, the drug has a limit that the body absorption is slow. The Institute is co-conducting research with Daewoong Pharmaceuticals to change the formulation of niklosamide to a smooth type of human absorption. The company was initially developing a new formulation of Niclosamide for incurable lung disease treatment.
Some companies have come out with stem cells. Song Soon-wook, Vice President of SCM Life Sciences, introduced the rationale and plan for the development of the stem cell therapy ‘SCM-AGH’ for corona 19 treatment. Already in China, a clinical trial was conducted for 10 corona 19 patients between the ages of 45 and 75 using a stem cell called ACE2-MSCs. In the trial, the researchers performed stem cell therapy for seven patients in the experimental group and three in the control group for a placebo treatment. Patients who received stem cells were given improvements in symptoms within 2-4 days. On the other hand, one person died in the control group, and two sustained symptoms. The researchers analyzed that stem cell therapy demonstrated the ability to protect lung cells, inhibit fibrosis of lung tissue, regenerate lung tissue, and regulate immune cells.
“We have a technology that can separate mesenchymal stem cells (MSC) from high purity,” Song said, “In a 2011 non-clinical study on pancreatitis treatment, we found that MSC reduces pancreatic enzymes and inflammatory cytokines, and increases anti-inflammatory cytokines.” “We observed that intravenously infused stem cells are distributed around the damaged pancreas,” he explained, “that is, if the stem cell therapy is injected intravenously into corona 19 patients, it can be inferred that the damaged organs will be found and distributed on their own.”
Some companies are looking forward to sepsis treatment. Ceo Cho Dae-woong Selibury announced the development of “ICP-NI” to fight acute inflammation of Corona 19. ICP-NI is a new drug severe sepsis to inhibit cytokine storm. Using ICP-NI, the company conducted non-clinical trials of acute hepatitis models, acute pneumonia models, and menopause models.
According to Cho, in the acute hepatitis model, no one was killed. In the pneumonia model, cytokines such as interrokines and interferon 6 were reduced by 79 to 128%, anti-inflammatory cytokines increased by 574%. In the pulmonary fibrosis model, cho explains that the lung tissue is protected close to its normal form. In addition, immune cell levels of the experiments dosing ICP-NI showed t cells 104%, CD4 + T cells 98%, B cells 96%, macrophages 104%.
Cho summarized the possibility of ICP-NI as reducing inflammation, protecting the lungs, suppressing cytokine storms, and maintaining the immune system. The company is conducting non-clinical trials to verify the safety of monkeys in order to develop this substance as a drug, and plans to complete non-clinical trials by the third quarter of this year.
A company that proposes corona19 treatment using gene therapy has also been suggested. Mr. Olix introduced the corona 19 RNA interference treatment development strategy. RNA interference technology is a small piece of SI RNA containing the protein information of the gene enters the cell, a principle to bind with the protein complex RISC. The binder cuts the mRNA to pass the gene information in the cell to block the expression of the virus. This technique is not limited to the gene structure because it acts only for the nucleotide sequence of the gene. That is, theoretically a technique that can develop a therapeutic agent for all genes.
“We have obtained several species of cp-asiRNA that can target coronavirus RNA,” lee said, “and we are working with our parent company in the United States to perform non-clinical trials to determine virus inhibition in the lung tissue of mice.” Regarding the treatment method, he said, “We are devising a method of injecting directly into the lung tissue of mice through airway intubation,” and “we plan to complete in vitro testing and non-clinical trials by the third quarter of this year.”
Copyright @ KUKINEWS. All rights reserved.