“RNA cap methylation in poxviruses and coronavirus – differences and similarities”

RNA methyltransferases (MTases) are responsible for synthesizing the 5′ RNA cap, which plays a crucial role in RNA stability and efficient translation. Over the past two years, both our research team and others have developed numerous inhibitors targeting coronaviral MTases. Through our efforts, we have successfully determined the crystal structures of these inhibitors bound to the coronaviral nsp14 and nsp16/nsp10 MTases. Additionally, we recently elucidated the crystal structure of the monkeypox virus MTase VP39, in complex with the broad-spectrum MTase inhibitor sinefungin and several other inhibitors. These structural studies have unveiled notable distinctions between coronaviral and poxviral MTases, while also highlighting the potential for targeting these enzymes with the same or closely related compounds.