Abstract: Compositions discussed herein are useful for treating a patient infected with a coronavirus, notably SARS-CoV-2 or COVID-19. The compositions to be administered to an infected patient utilize inhibitors of SARS-CoV-2 papain-like protease (PLpro). Several of these inhibitors include available hepatitis C virus (HCV) drugs that are already FDA-approved. These PLpro inhibitors have been found to be strongly synergistic with inhibitors of SARS-CoV-2 polymerases, such as RNA-dependent RNA polymerase (RdRp). One such polymerase inhibitor, remdesivir, is already in use as an anti-viral treatment of patients with COVID-19. The PLpro inhibitors, including repurposed HCV drugs such as grazoprevir, vaniprevir, and paritaprevir, increase remdesivir's ability to suppress coronavirus replication antiviral activity as much as 10-fold.

Abstract: The invention provides a target and methods for specific binding and inhibition of RlmA proteins from bacterial specie The invention is directed to a method for identifying compounds that bind to a bacterial RlmA-binding pocket, comprising preparing a reaction solution comprising the compound to tested and an entity comprising a bacterial RlmA-binding pocket and detecting presence or amount of binding. The invention has applications in control of bacterial gene expression, control bacterial growth, antibacterial chemistry, and antibacterial therapy.