The nonstructural protein 5 (nsp5, also known as 3CLpro), is the main protease of the coronavirus genome, exhibiting as main known role the cleavage of the polyproteins translated from the viral RNA viral. Dimerization of SARS-CoV-1 3CLpro is essential to stabilize the catalytic site. The dimer interface is highly conserved within SARS-CoV-1 and -CoV-2, however, substitutions may affect dimer interaction and phosphorylation pattern of 3CLpro in SARS-CoV-2. Given that the substrate binding site of SARS-CoV-2 3CLpro is very similar to PEDV 3CLpro, it is possible that SARS-CoV-2 3CLpro is also active towards NF-kB essential modulator, thus suppressing host immune response.