Author summary Zoonotic transmission occurs when viruses ‘jump’ from animals into human. This may lead to viral outbreaks such as the Covid-19 pandemic, posing a significant threat to public health.
The SARS-CoV-2 main protease specifically cleaves a conserved sequence in the human tRNA modifying enzyme TRMT1, resulting in reduced tRNA binding and the complete loss of TRMT1-mediated tRNA methyltransferase activity.