New drug applicant against the novel coronavirus
A team of scientists from China has found a fresh prospect drug against the novel coronavirus, SARS-CoV-2, which functions by inhibiting a key the main virus’s machinery.
A lot of the world is on hold until scientists discover a vaccine for the novel coronavirus, which includes, so far, claimed thousands of lives.
However, with current estimates suggesting a vaccine is 12-18 months away, many persons are putting increasing hope on an efficient treatment for COVID-19.
For this reason, persons have already been eagerly awaiting news on Gilead’s experimental Ebola drug remdesivir, after former World Health Organization (WHO) Assistant Director-General Bruce Aylward described it as the only drug that the business consider to have “real efficacy.”
However, with an increase of recent data appearing to show failure in a clinical trial, the race for an effective treatment for COVID-19 continues.
Structure-based design
The scientists behind the current study - which features in Science - took a structure-based method of designing cure, using the major parts of the coronavirus as a starting point. The virus contains genetic information in RNA, which sits within an envelope of fats and proteins.
These proteins belong to four main classes, relating to:
- the envelope (E) and membrane (M), which surround the virus
- spike (S) proteins, which are protrusions that bind to receptors on the host cell
- the nucleocapsid (N), which protects the virus’s genetic information
The production of these viral proteins occurs by making use of a specialized enzyme called a protease.
This enzyme is an ideal target for a drug since it plays a vital role in the life cycle of the virus, helping it replicate. Put simply, the virus cannot live without it.
Lead compounds
The scientists analyzed the coronavirus protease at length to help them identify compounds that target a crucial part of its structure.
Beginning with a starting material that is available from commercial suppliers, they performed a number of synthesis steps to create two lead compounds named 11a and 11b.
The scientists discovered that both compounds were good inhibitors of the enzyme, achieving 100% and 96% inhibition activity, respectively.
The scientists continued to monitor the antiviral activity of the compounds using infected cells, and again, both drugs showed good anti-infection activity.
They then used mice to research the pharmacokinetics, which identifies how the body absorbs the drug and breaks it down over time. This analysis gives a sign of how long the drug remains active in the body, and, therefore, what dosages could be safe and effective.
The team administered the two compounds by various routes, including injection just under your skin and intravenous (IV) delivery. Giving the compound via an IV drip could be necessary in some extreme cases of COVID-19 to accomplish a higher concentration rapidly.
Both compounds showed good pharmacokinetic properties, suggesting that they could both be promising drug candidates.
Fast tracking development
To investigate how the compounds work, the scientists used high resolution imaging techniques. These studies showed that the compounds have similar mechanisms of action, both binding to the same key structure of the enzyme to block its activity and, thus, kill the virus.
Although both compounds showed favorable properties, final tests in animals showed that the first compound, 11a, is less toxic, which makes it the better candidate.
In line with the reported results, that is an extremely promising compound. Furthermore, since there is no human equivalent to the enzyme that it targets, the drug is unlikely to cause serious side effects in people.
The researchers say that preclinical research on the compound is continuing. Also, they are sharing their data with scientists all over the world to greatly help accelerate the development of the treatment.
Source: www.medicalnewstoday.com
