Russian medical staff watching corona19 patients. AP/Yonhap News
While there is no new coronavirus infection (COVID-19, corona19) treatment yet, many pharmaceutical companies and research institutes are working to develop a therapeutic agent. To change the use of existing drugs, or to find a new drug based on the characteristics of sascoronavirus-2 (SARS-CoV-2) causing corona 19 is mainly used. However, as of at least early April, experts have suggested that there are no treatments that can be effective.
James Sanders, a professor at the University of Texas School of Medicine, published a review paper on the development of the iconic Corona19 drugs currently being developed and the effects identified so far in the journal Jama. According to him, a total of 291 clinical trials as of february 2 have been conducted or completed for Corona 19, of which 109 are drug drug trials. However, there is no treatment that has been confirmed to be effective yet.
The team examined the status of corona 19 when the existing therapeutic agent was repurposed for Corona 19, and divided into candidates that are being developed in corona 19. This paper and other recently published studies have compiled a summary of the status of leading therapeutics.
●Chloroquine and hydrochloroquine: Safe but effective
A representative case of a re-creation drug to repurpose existing drugs is chloroquine and hydroxy chloroquine, a malaria treatment. The virus blocks the process of fusion with cell membranes to penetrate human cells.
The researchers said, “The Chinese research team prescribed this drug to see the effects of viral reduction and disease mitigation, but it was not a co-evaluation claim, and there is no reliable evidence that it is effective in severe acute respiratory syndrome (SARS, SARS) or Middle East Respiratory Syndrome (MERS). In a small clinical trial of 36 people in France, the virus-free detection rate after 6 days of dosing was significantly higher than if the drug did not dosing, but the effect was higher if the co-dosing of azithromycin (graph below), but a small clinical patient did not even know who was dosing or did not know the patient did not know the patient was determined to be incomplete results.
A graph by a French team that tracked the detection rate of viruses in the specimens of corona 19 patients. When receiving the malaria drug chloroquine (hydrochloroquine) compared to the average patient, the virus detection rate fell quickly, the parallel dosing of ajidromycin reported that the virus detection almost disappeared in six days. It is a small-scale trial of more than 20 patients and has not been published as a formal clinical paper. Provided by The University Hospital Research Institute for Mediterranean Infectious Diseases in France
It did not work in a randomized trial of 30 people in China. The appropriate dosage has not yet been determined, further research is needed. There were no special side effects, and the results of the dosing on 588 pregnant women in 12 studies seemed to be safe for pregnant women.
●Caletra: The results are weak compared to popularity
The HIV drug Calletra (Lofinavir-Ritonavir complex) is also widely expected after corona19. The virus penetrates into the human cells and then produces proteins using their genetic material, and then uses them to create replication and transcription enzymes to produce genetic material replication and shell proteins. In this process, a protease is required to make an enzyme, blocking the enzyme to prevent proliferation.
According to the researchers, Caletra has no cell test results for corona 19. In coronavirus was mainly sass target studies were made, but lowered the mortality rate is effective until the initial 7-10 days of infection, and since the dosing was not effective. A chinese research team conducted a clinical trial of 199 patients in the journal New England Journal of Medicine on March 18, but it did not show much effect (graph below). There is also a reason that the lieutenant dosing time is 13 days late, but there was no significant effect on patients who took the medication sooner than that. “Additional clinical trials are taking place, but their role as corona19 therapeutic agent is limited,” the researchers said.
Small clinical trials of calletra (lofinavir-ritonavir), which is widely used as a treatment for Corona19, have been reported to have no significant effect. The graph is to express the degree of clinical symptom improvement, there is no significant difference between the dosing group and the control group. Courtesy of NEJM
●Ribavirin: Toxicity, low effectiveness, sokbin gangjeong
Ribavirin is an analog with a structure similar to guanine (G) of the genetic material of the virus. When the virus replicates or transcriptions the genetic material RNA enters instead of guanine to stop replication. It’s like putting a diesel on a gasoline car to stop the engine.
The researchers noted, “The disadvantage is that this drug must be administered at high concentrations in order to have a replication stoppage effect in trials targeting coronavirus.” The researchers reviewed 30 studies that tested ribavirin on sas, 26 were difficult to draw conclusions, and four concluded that they were dangerous because of side effects such as hepatotoxicity and hemolytic anemia. Sas patients with high doses 60% experienced hemolytic anemia. Transmaminase levels are 75%, especially mers studies were also not clear lysita virus removal. The researchers concluded that “the therapeutic effect of coronavirus is unclear and the potential toxicity is high, and the value of corona19 is not very valuable as a therapeutic agent.”
●Remdesivir: A candle of hope that is still not extinguished. But optimism is forbidden
It is the most notable candidate in the Corona 19 crisis. It is an antiviral agent of the principle that prevents the growth of the virus by interfering with replication with rna salt analogs similar to ribavirin. Originally developed for Ebola, it was scrapped in Clinical Phase 3 and re-attracted attention as Corona 19.
Recently, a promising clinical trial was presented with intracellular penetration of sascoronavirus-2 the candidate for the corona 19 therapeutic agent that is being conducted. Although we want to prevent the activity of the virus with a variety of strategies, the reality is that there are no candidates for a therapeutic agent that has a solid effect yet. Shin Young Yoon
The most notable reason is that the antiviral effect has been demonstrated in cell studies. Ec50 concentration required to reduce the virus-infected cells in half in cell experiments is very low (0.77 micromoly). It means that it produces a high antiviral effect with a small amount of dosing. Hydrochloroquine is a figure of 6.14 micro-moles, chloroquine is 23.9 micro-moles. This means that each produces one-eighth and one-third the effect of remdesivir. The researchers argued that a number of clinical trials are underway and are promising, and that the U.S. Food and Drug Administration (FDA) should allow the drug to be approved for use in a compassionate use approval plan that allows for end-stage patients without alternatives.
On November 11, the New England Journal of Medicine published the results of the study of 53 people around the world, following the approval of the compassionate use of Remdesivir. Here, 68% of the total patients saw a clinical effect, such as improved breathing. The 18-day rate of life was 13%. “Compared to 22% in other clinical trials involving respiratory patients with weaker symptoms, the 13% critical rate is notable, even in situations where the rate of severe abnormalities, such as respiratory intubation and the use of in vitro oxygen supply equipment (Ekmo), was high,” the researchers said. However, the patient group is different and it is not possible to directly compare, it was not confirmed that the antiviral effect did not have a virus test. The number of patients in the experiment is small, and the study, sponsored by Gilliard Sciences, which manufactures Remdesivir, has the limitation that the results should be interpreted.
●Other candidates: It is still vague and requires further research
Paifiravir is a similar body that interferes with the replication and transcription of viral genetic material similar to ribavir or remdesivir. Ec50 is measured at 61 in cell experiments, the antiviral effect is as low as about one-90th of the level compared to remdesivir. In a clinical trial involving 120 patients with moderate symptoms, the recovery rate was increased. However, it did not have a significant effect on severe patients.
Omiphenovir (Abidol) is not yet data-worthy, but it has been classified as a drug that can be expected for subsequent clinical trials. In a small, non-randomized study involving 67 people, the mortality rate was lowered nine days later. However, the evidence is not yet solid and we have to wait for the results of subsequent clinical studies in China.
On the other hand, corona 19 therapeutic trial showed that it is currently taking place in various stages. 1 09 drug drug clinical trials to diagnose the side effects of the drug phase 1 4 cases, check the effect on the effect of dozens to 100 people and two phases to determine the appropriate dosing concentration was conducted 36 cases or proceeded. There were 36 cases for a large population, and 11 were already in the top four, monitoring the drugs that were commercialized after the three phases had already been completed.