SARS-CoV-2 nsp7 and nsp8 are important cofactors of the RTC, as they interact and regulate the activity of RNA-dependent RNA polymerase and other nspsHere we used solution-based structural proteomic techniques, hydrogen-deuterium exchange mass spectrometry (HDX-MS) and crosslinking mass spectrometry (XL-MS), illuminate the dynamics of SARS-CoV-2 full-length nsp7, nsp8, and nsp7:nsp8 proteins and protein complex.