During coronavirus infection, viral mRNA generates polyproteins pp1a and pp1ab, cleaved by the main protease (Mpro) to produce nonstructural proteins (nsps). These nsps form the replication-transcription complex for viral RNA replication. Understanding Mpro's cleavage order is crucial for antiviral development. AlphaFold3 predictions reveal structural variability in nsp recognition sites, influencing accessibility and binding to Mpro. This variability may affect cleavage efficiency, impacting viral replication. These insights support improved antiviral strategies.