Thwarting coronaviruses by preventing them from copying themselves

What if a single drug treatment could thwart not only the current outbreak of the coronavirus COVID-19, but also similar viruses that cause everything from the common cold to foot and mouth disease? Scientists at the University of Lubeck in Germany believe it’s possible, and they say have enough evidence from cell-based studies to move one promising compound into animal trials.

The German team found two molecules that target a protein-cutting enzyme that many viruses, including COVID-19, need to replicate. In cell studies, one of the compounds blocked multiple coronaviruses and enteroviruses, including the pathogen that caused the 2003 SARS outbreak, and the other was effective against MERS, they reported in the journal of Medicinal Chemistry.

The researchers started by studying X-ray crystal structures of protein-cutting enzymes, which are also referred to as proteases. Then they made several compounds from alpha-ketoamide, predicting that some of them would lock into the proteases’ active sites, thereby preventing them from functioning. They now plan to move the most promising compound, which they dubbed 11r, into animal studies.

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COVID-19’s spread continues to raise concerns around the world, as biopharma companies race to develop drugs and vaccines against the virus. More than 46,000 people have contracted the Wuhan coronavirus, which has caused 1,300 deaths, according to recent figures from the World Health Organization. And yesterday, the Centers for Disease Control confirmed that a patient in California contracted the virus despite not having traveled to an affected country or coming in contact with an infected patient.

Earlier this week, Moderna said it’s getting ready to start a clinical trial of its messenger RNA (mRNA) vaccine, mRNA-1273, in the treatment of COVID-19. And Gilead has started testing its failed Ebola drug remdesivir in COVID-19.

The University of Lubeck researchers are working with scientists from China, the Netherlands and Belgium in developing alpha-ketoamides as broad-spectrum treatments for coronaviruses and enteroviruses. Because all of these viruses have similar protein-cutting enzymes, they hope their work will prove useful in the development of future treatments for COVID-19. Their plan is to first test 11r in animal models of MERS and coxsackievirus-induced pancreatitis before moving it into further studies.

“Because of the high similarity between the main proteases of SARS-CoV and the novel BetaCoV/Wuhan/2019, we expect 11r to exhibit good antiviral activity against the new coronavirus as well,” they wrote in the study.