Globally, more than 1.3 million people have been confirmed with the new coronavirus. A few hours earlier, British Prime Minister Boris Johnson was in intensive care… Unfortunately, we don’t yet have an effective treatment against the new coronavirus. Some potential candidate drugs are either compromised in clinical trials or are still awaiting the results of clinical trials.
Some infectious disease experts point out that using existing “old medicines” to treat brand new viruses is somewhat of luck-sydsetting. Even if it works well, it may not be able to fight other coronaviruses that may occur in the future. To this end, these experts called on the pharmaceutical industry to develop “broad-spectrum antiviral drugs”, is expected to respond to future outbreaks of coronavirus.
The “broad-spectrum antiviral drug” was reported today in Science Translational Medicine, a sub-journal of the leading academic journal Science. It not only significantly inhibits the replication of new coronaviruses in human cells, but also effectively suppresses SARS and MERS viruses in mouse models. More crucially, the drug has the potential to be taken orally. In general, the advantage of oral drugs is that infected people do not have to take the risk of going to the hospital for injections, and can be treated at home. The authors say the study highlights the potential antiviral effects of the treatment for new coronaviruses, as well as other zoonotic co-strains.
The drug, called EIDD-1931 (also known as nHC), is a nucleotide analogue analogue. Its potential principle is that it causes mutations within the virus, preventing the virus from surviving. Previously, it has demonstrated antiviral activity in a variety of RNA viruses, including influenza viruses and Ebola viruses. It is worth mentioning that there is not much kinship between these viruses, which also indicates the molecular’s broad-spectrum antiviral activity. To understand the molecular anti-viral potential on new coronaviruses and other coronaviruses, the researchers conducted a series of tests.
In cell experiments, the molecule can effectively inhibit the replication of neo-coronaviruses, SARS viruses, and MERS viruses (Photo: Resources 1)
In human primary airway epithelial cells, the researchers first confirmed that eIDD-1931 at higher concentrations (100 sM) did not cause significant changes in cell gene expression, supporting its safety to some extent. The researchers then found that the molecule was effective in the epithelial cells of the airways to reduce replication of the new coronavirus, SARS virus, and MERS virus. The authors note that this suggests that within the cell line, EIDD-1931 has effective antiviral activity without causing cytotoxicity.
Interestingly, the molecule appears to be able to suppress some mutated coronaviruses. Another popular antiviral drug, remdesivir, targeted the RdRp target, which can significantly reduce redsieve’s vitality when two specific mutations occur, the researchers note. But the two mutated drug-resistant strains have become more sensitive to EIDD-1931. This shows that EIDD-1931 and Redsiewe each have unique mechanismofs of action, there may be complementary effects.
Molecular structure of EIDD-2801 (Image Source: Resources 2)
After positive results in in vitro experiments, the researchers decided to turn their attention to the body. In order to improve pharmacokinetics and oral accessibility in animals, this time they used the precursor drug EIDD-1931 (called EIDD-2801, which can be taken orally). In the mouse model, the plasma characteristics of the two are very close.
The study found that eIDD-2801 significantly reduced weight loss in mice and reduced lung bleeding in mouse models infected with SARS-MA15, a mouse SARS virus. In addition, the level of SARS virus in the lungs also decreased with the increase in drug concentration, showing dose dependence. And after infection, the earlier you use it, the better the effect looks. In mice infected with the MERS virus, scientists observed similar results.
The sooner you use it after infection, the better the effect looks (Image Source: Resources)
Taken together, the researchers concluded their paper by noting that the data support edding eIDD-2801. This broad-spectrum antiviral drug is expected not only to treat the current coronavirus, but also to treat future coronavirus infections. The study was also very concerned by the academic community, and the American Chemical Society’s C and EN also contributed to the study. But we also need to note that, unlike Redsey, we don’t yet have human security data for EIDD-2801. Earlier, the company with the right to develop the drug announced that it would communicate with the FDA as soon as possible to discuss clinical trials. Today, the FDA also announced that it has officially approved EIDD-2801 for human clinical trials.