“…The viral-RNA replication mechanism is complex, involving RNA synthesis, proofreading, and capping and is mainly carried out by the mini-replication transcription complex plus error correction machinery (mRTC+ECM from here on referred to as RTC), having to survive against the human immune response. Cryo-EM techniques and computational methods have been immensely helpful in elucidating the overall structural organization of the RTC (Chen et al, 2020, Perry et al, 2021, Yan et al, 2020, 2021a), but the high intrinsic flexibility, size and complexity of the nsp arrangement entails that the overall resolution of the data is inherently poor. Consequently, the structure refinement workflows discard 30-40% of collected images from the existing RTC complex datasets (Chen et al, 2020, Yan et al, 2020, 2021a), leaving significant gaps in our understanding.…”