发布时间:
2021-05-11 00:00:00
期刊:
PNAS
doi: 10.1073/pnas.2102516118
作者:
Brandon Malone,James Chen,Qi Wang,Eliza Llewellyn,Young Joo Choi,Paul Dominic B. Olinares,Xinyun Cao,Carolina Hernandez,Edward T. Eng,Brian T. Chait,David E. Shaw,Robert Landick,Seth A. Darst,Elizabeth A. Campbell
摘要:
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome is replicated and transcribed by its RNA-dependent RNA polymerase (RdRp), which is the target for antivirals such as remdesivir. We use a combination of approaches to show that backtracking (backward motion of the RdRp on the template RNA) is a feature of SARS-CoV-2 replication/transcription. Backtracking may play a critical role in proofreading, a crucial process for SARS-CoV-2 resistance against many antivirals.
The cryo-EM density maps have been deposited in the EMDataBank: EMD-23007 (nsp131-BTC5), EMD-23008 (nsp132-BTC5), and EMD-23009 [BTC5(local)]. Atomic coordinates have been deposited in the Protein Data Bank: [7KRN][1] (nsp131-BTC5), [7KRO][2] (nsp132-BTC5), and [7KRP][3] [BTC5(local)]. The molecular dynamics trajectories described in this work are available at [https://www.deshawresearch.com/downloads/download\_trajectory\_sarscov2.cgi/][4].
[1]: http://www.rcsb.org/pdb/explore/explore.do?structureId=7KRN
[2]: http://www.rcsb.org/pdb/explore/explore.do?structureId=7KRO
[3]: http://www.rcsb.org/pdb/explore/explore.do?structureId=7KRP
[4]: https://www.deshawresearch.com/downloads/download_trajectory_sarscov2.cgi/