September 12, 2022 -- Mount Sinai researchers have produced a high-resolution crystal structure of an enzyme that is essential to the survival of SARS-CoV-2. The finding could lead to more antivirals to combat current and future coronaviruses, they added.
The scientists developed three crystal structures of coronavirus nonstructural protein 14, which contains the RNA methyltransferase domain (Nat Struct Mol Bio, September 8, 2022). They used fusion-assisted crystallization, which fuses the enzyme with another small protein that helps it to crystalize.
In terms of developing antivirals, each crystal structure had different cofactors, and the researchers identified the best scaffold for the design of antivirals that would inhibit RNA methyltransferase activity. The antiviral takes the place of the natural cofactor S-adenosylmethionine and prevents the methyltransferase chemistry from occurring. Doing so means the coronavirus is unable to survive.
The research paves the way for designing more broad-spectrum antivirals that include small molecule inhibitors.