美国洛克菲勒大学Elizabeth A. Campbell、Seth A. Darst等研究人员合作，解析出SARS-CoV-2复制-转录复合物中解旋酶-聚合酶偶联的结构基础。相关论文于2020年7月28日在线发表于《细胞》。
Title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex
Author: James Chen, Brandon Malone, Eliza Llewellyn, Michael Grasso, Patrick M.M. Shelton, Paul Dominic B. Olinares, Kashyap Maruthi, Ed T. Eng, Hasan Vatandaslar, Brian T. Chait, Tarun Kapoor, Seth A. Darst, Elizabeth A. Campbell
Abstract: SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp82/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The Nidovirus-order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12-thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg2+ bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapeutic development.