Fig. 1: Cryo-EM structure of the RTC with bound RNA and AT-9010 molecules and corresponding cryo-EM map.
From: A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase
a Structure of the guanine analog phosphoramidate prodrug AT-527 (left) and its active triphosphate form AT-9010 (right) following activation by cellular kinases. b Ribbon and stick representation of the cryo-EM structure of nsp7-(nsp8)2-nsp12:AT-9010-terminated-RNA:(AT-9010)2 complex. RNA, AT-9010 and protein shown with the following colors: template RNA, green; RNA product, orange; AT-9010, magenta; nsp7, pink; nsp81 and nsp82, yellow and cyan respectively; and nsp12 in gray and blue for NiRAN and RdRp domains respectively. c Brown and black ovals are enlarged for RdRp domain and NiRAN domains, respectively, showing experimental cryo-EM map around AT-9010, In the RdRp, one AT-9010 monophosphate (AT-9010-MP) is incorporated at (+1) position, with an incoming AT-9010 occupying the (−1) position. In the NiRAN domain, AT-9010 is bound it its diphosphate form (AT-9010-DP). d Experimental cryo-EM map for RNA (stick representation), showing incorporated AT-9010-MP (+1) and incoming AT-9010 (−1). Bases of the template RNA involved in the interaction with AT-9010 are numbered as C24–C27. All cryo-EM maps are represented at 3.5σ representative of the general map of the entire complex at 2.98 Å resolution.
