The coronavirus (CoV) disease 2019 (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a worldwide pandemic. The 3C-like protease (3CL^{pro} ), which cleaves 11 sites including its own N- and C-termini on the viral polyproteins, is essential for SARS-CoV-2 replication. In this study, we constructed the full-length inactive 3CL^{pro} with N- and C-terminal extensions as substrates for monitoring self-cleavage by wild-type 3CL^{pro} . We found that the rate-limiting C-terminal self-cleavage rate of SARS-CoV-2 3CL^{pro} was 35-fold faster than that of SARS-CoV 3CL^{pro} using the Trx/GST-tagged C145A 3CL^{pro} substrates. Since self-cleavage of 3CL^{pro} is the initial step for maturation of other viral proteins, our study suggests more facile SARS-CoV-2 replication than that of SARS-CoV.
【저자키워드】 COVID-19, SARS-CoV-2, 3CLpro, maturation, self-cleavage.,