A team of scientists has engineered antiviral compounds that can kill several types of coronaviruses, including SARS-CoV-2, the virus that causes COVID-19. The compounds neutralized viruses in human airway cells and improved survival in mice infected with a deadly, closely related virus that causes Middle East respiratory syndrome (MERS). The new compounds' broad activity suggest that they should be further developed as treatments for infections with emerging coronaviruses, which currently have few effective antivirals and no approved vaccines. Although many coronaviruses cause only mild cases of the common cold, emerging species such as SARS-CoV-2 and SARS-CoV (the cause of the 2003 SARS outbreak) pose a serious risk to global health and security. The spread of SARS-CoV-2 has caused one of the most dangerous pandemics in modern history, and infections with its cousin MERS-CoV have a fatality rate of almost 35%, according to the World Health Organization. In previous work, Athri Rathnayake and colleagues had developed a series of antiviral compounds named 3C-like protease inhibitors, which target an enzyme essential to the replication of coronaviruses. Here, they tested several 3C-like protease inhibitors in cells infected with SARS-CoV-2, SARS-CoV, or MERS-CoV. One of the compounds, named 6e, showed strong activity against SARS-CoV-2 and inhibited viral replication by tenfold in cultured human airway epithelial cells taken from infected donors. Another potent compound named 6j boosted the odds of survival in mice infected with MERS-CoV, slashed the amount of virus in the lungs, and prevented dangerous complications like lung edema. Rathnayake et al. plan to conduct further research to see whether one of their compounds could effectively treat both MERS and COVID-19 in humans.