Globally, the number of confirmed infections in COVID-19 has exceeded 654.38 million+300,000. A few hours ago, British Prime Minister Boris Johnson was admitted to the intensive care unit. Unfortunately, so far, we have no effective treatment for COVID-19. Some potential candidate drugs have either failed in clinical trials or are still waiting for the results of clinical trials.
Some infectious disease experts point out that it is a bit lucky to treat a brand-new virus with existing "old drugs". Even if it can achieve good results, it may not be able to fight other coronaviruses that may appear in the future. To this end, these experts called on the pharmaceutical industry to develop "broad-spectrum antiviral drugs", which is expected to cope with the future coronavirus epidemic.
Today, Scientific Translational Medicine, a sub-issue of the top academic journal Science, reported such a "broad-spectrum antiviral drug". It can not only significantly inhibit the replication of COVID-19 in human cells, but also effectively inhibit SARS virus and MERS virus in mouse models. More importantly, this drug has the potential of oral administration. Generally speaking, the advantage of oral drugs is that infected people can be treated at home without taking the risk of going to the hospital for injections. According to the author, this study highlights the potential antiviral effect of this therapy in treating coronavirus in COVID-19 and other people and animals.
This drug is called EIDD- 193 1, which is a nucleotide analogue. Its basic principle is to cause virus mutation, so that the virus can not survive smoothly. Previously, it showed antiviral activity in various RNA viruses such as influenza virus and Ebola virus. It is worth mentioning that there are not many genetic relationships between these viruses, which also shows the broad-spectrum antiviral activity of this molecule. In order to understand the antiviral potential of this molecule against COVID-19 and other coronaviruses, researchers conducted a series of tests.
▲ This molecule can effectively inhibit the replication of COVID-19 virus, SARS virus and MERS virus in cell experiments.
In human primary airway epithelial cells, the researchers confirmed for the first time that higher concentrations of EIDD- 193 1 did not cause obvious changes in cell gene expression, which supported its safety to some extent. Subsequently, researchers found that this molecule can effectively reduce the replication of COVID-19, SARS virus and MERS virus in respiratory epithelial cells. The author points out that this shows that EIDD- 193 1 has effective antiviral activity in this cell line without causing cytotoxicity.
Interestingly, this molecule seems to be able to inhibit some mutated coronaviruses. The researchers mentioned in the article that another antiviral drug, Remdesivir, is targeted at the RdRp target. When there are two specific mutations in this target, the activity of Remdesivir will be greatly reduced. However, drug-resistant virus strains with these two mutations become more sensitive to EIDD- 193 1. This shows that EIDD- 193 1 and raldesivir have their own unique mechanisms of action and may have complementary effects.
▲ the molecular structural formula of ▲EIDD is -280 1
After the positive results in vitro experiments, the researchers decided to turn their attention to the human body. In order to improve the pharmacokinetics and oral administration route of animals, this time they used the prodrug of EIDD- 193 1. In the mouse model, the plasma characteristics of the two are very close.
It was found that in the mouse model infected with SARS-MA 15, EIDD-280 1 significantly reduced the weight loss of mice and reduced pulmonary hemorrhage. In addition, the level of SARS virus in the lung also decreased with the increase of drug concentration, showing a dose dependence. And the sooner you use it after infection, the better the effect seems to be. Scientists have also observed similar results in mice infected with MERS virus.
▲ The sooner you use it after infection, the better the effect seems to be.
Based on these results, the researchers mentioned at the end of the paper that these data support the further development of EIDD-280 1. This broad-spectrum antiviral drug is expected to treat not only current coronavirus, but also future coronavirus infection. Academic circles are also very concerned about this research, and CEN, a subsidiary of the American Chemical Society, also made a special report on this research. However, we also need to note that, unlike Remdesivir, we don't have the human safety data of EIDD-280 1. Previously, the company with the right to research and develop this drug announced that it would communicate with the US FDA as soon as possible to discuss clinical trials. Today, FDA also announced the official approval of EIDD-280 1 for human clinical trials.
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