A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus fulllength nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified βhairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.

Transcription of SARS-CoV-2 mRNA requires sequential reactions facilitated by the r eplication and t ranscription c omplex (RTC). Here, we present a structural snapshot of SARS-CoV-2 RTC as it transition towards cap structure synthesis. We determine the atomic cryo-EM structure of an extended RTC assembled by nsp7-nsp8 2 -nsp12-nsp13 2 -RNA and a single RNA binding protein nsp9. Nsp9 binds tightly to nsp12 (RdRp) NiRAN, allowing nsp9 N-terminus inserting into the catalytic center of nsp12 NiRAN, which then inhibits activity. We also show that nsp12 NiRAN possesses guanylyltransferase activity, catalyzing the formation of cap core structure (GpppA). The orientation of nsp13 that anchors the 5’ extension of template RNA shows a remarkable conformational shift, resulting in zinc finger 3 of its ZBD inserting into a minor groove of paired template-primer RNA. These results reason an intermediate state of RTC towards mRNA synthesis, pave a way to understand the RTC architecture, and provide a target for antiviral development.

Non-structural proteins (nsp) constitute the SARS-CoV-2 replication and transcription complex (RTC) to play a pivotal role in the virus life cycle. Here we determine the atomic structure of a SARS-CoV-2 mini RTC, assembled by viral RNA-dependent RNA polymerase (RdRp, nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2), by cryo-electron microscopy. Two groups of mini RTCs with different conformations of nsp13-1 are identified. In both of them, nsp13-1 stabilizes overall architecture of the mini RTC by contacting with nsp13-2, which anchors the 5′-extension of RNA template, as well as interacting with nsp7-nsp8-nsp12-RNA. Orientation shifts of nsp13-1 results in its variable interactions with other components in two forms of mini RTC. The mutations on nsp13-1:nsp12 and nsp13-1:nsp13-2 interfaces prohibit the enhancement of helicase activity achieved by mini RTCs. These results provide an insight into how helicase couples with polymerase to facilitate its function in virus replication and transcription.

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Metallic anodes have high theoretical specific capacities and low electrochemical potentials. However, short-circuit problems caused by dendritic deposition and low Coulombic efficiency limit the cyclic life and safety of metallic anode-based batteries. Herein, dendrite-free and flexible three-dimensional (3D) alkali anodes (Li/Na-Ti 3 C 2 T x -rGO) are constructed by infusing molten lithium (Li) or sodium (Na) metal into 3D porous MXene Ti 3 C 2 T xreduced graphene oxide (Ti 3 C 2 T x -rGO) membranes. Firstprinciples calculations indicate that large fractions of functional groups on the Ti 3 C 2 T x surface lead to the good affinity between the Ti 3 C 2 T x -rGO membrane and molten alkali metal (Li/Na), and the formation of Ti-Li/ Na, O-Li/Na, and F-Li/Na mixed covalent/ionic bonds is extremely critical for uniform electrochemical deposition. Furthermore, the porous structure in Li/Na-Ti 3 C 2 T x -rGO composites results in an effective encapsulation, preventing dendritic growth and exhibiting stable stripping/plating behaviors up to 12 mA•cm −2 and a deeper capacity of 10 mA•h• cm −2 . Stable cycling performances over 300 h (750 cycles) at 5.0 mA•cm −2 for Li-Ti 3 C 2 T x -rGO and 500 h (750 cycles) at 3.0 mA•cm −2 for Na-Ti 3 C 2 T x -GO are achieved. In a full cell with LiFePO 4 cathodes, Li-Ti 3 C 2 T x -rGO electrodes show low polarization and retain 96.6% capacity after 1000 cycles. These findings are based on 2D MXene materials, and the resulting 3D host provides a practical approach for achieving stable and safe alkali metal anodes. KEYWORDS: MXene-Ti 3 C 2 T x , 3D porous film, first-principles calculations, metal anodes (Li/Na), thermal infusion, encapsulation effect