According to a March 2 report from the World Health Organization, there have been 88,948 confirmed cases of the Wuhan coronavirus worldwide. It has spread to 65 countries now and caused over 3,000 deaths since the first cases in Wuhan, China, merely three months prior in December 2019.
Naturally, researchers are working around the clock to find a way to stop the sickness from spreading via vaccine and a treatment for those that are already infected. The latest breakthrough involves a team of scientists who designed compounds that can block the replication of coronaviruses and other disease-causing viruses. These compounds have so far only been tested in the lab. The research has been published in ACS’ Journal of Medicinal Chemistry.
The Wuhan coronavirus (COVID-19, SARS-CoV-2, or 2019-nCoV) is related to (but not the same as) the Middle-East respiratory disease virus (MERS-CoV) that materialized in 2012, and the severe acute respiratory syndrome (SARS) virus that spurred an outbreak in 2003 (SARS-CoV-1). They all inflict the same flu-like symptoms that often lead to pneumonia.
Up until the most recent strain, SARS-CoV-2, the number of cases remained relatively small – not enough to warrant large expenditures by pharmaceutical companies to hunt for a cure. Therefore, no effective treatment was ever developed. Now the situation is much different, but fortunately, Hong Liu, Rolf Hilgenfeld, and colleagues may have a solution.
The team aimed to develop a broad-spectrum antiviral drug that could target all the coronaviruses, as well as enteroviruses, which cause illnesses such as the common cold, the “summer flu,” and, hand foot and mouth disease. The reason the scientists knew they could link all these viruses to one cure is that they all share a similar protein-cutting enzyme that is essential for viral replication.
The enzyme is called the “main protease” in coronaviruses and the “3C protease” in enteroviruses. By examining the X-ray crystal structures of the proteases, the team was able to make a series of α-ketoamide compounds designed to fit snugly into the enzymes’ active sites and thus interfere with their function. After creating a variety of designs, they took the molecules into the lab and tested each one in test tubes and Petri dishes filled with human cells.
Of the lot, they identified the winner molecule – one versatile inhibitor that blocked multiple coronaviruses and enteroviruses, including SARS-CoV-1. The next phase of their investigation will be to test the inhibitors in small-animal models of disease.
