A wrench in the works of COVID-19: Understanding the inner workings of the virus that causes coronavirus disease 2019 (COVID-19) may help us to disrupt it. Yin et al. focused on the viral polymerase essential for replicating viral RNA. They determined a structure of the polymerase bound to RNA and to the drug remdesivir. Remdesivir mimics an RNA nucleotide building block and is covalently linked to the replicating RNA, which blocks further synthesis of RNA. The structure provides a template for designing improved therapeutics against the viral polymerase. Science , this issue p. 1499

COVID-19 is caused by SARS-CoV-2. 1 As of July 16th, 2020, there were 13,579,581 diagnosed cases and 584,782 deaths attributed to COVID-19 reported globally (https://coronavirus.jhu.edu/map. html). 2 Unfortunately, there is still no effective drug or vaccine for treating this disease. To accelerate drug development, there is an urgent need to identify critical molecular targets and the role they play in infection. Herein, we reported that Orf9b localizes on the membrane of mitochondria and suppresses type I interferon (IFN-I) responses through association with TOM70, and TOM70 overexpression could largely rescue this inhibition. Our results suggest the potential of targeting Orf9b-TOM70 interaction as a novel therapeutic strategy of COVID-19. Induction of IFN-I is a central event of the immune defense against viral infection. 3 Upon exposure to RNA viruses, an intracellular antiviral response is initiated by activation of RIG-I like receptors. In particular, when RIG-I/MDA5 detects viral RNA, they trigger a signaling complex on the mitochondrial outer membrane, including the adapter proteins MAVS/TRAF3/TRAF6/TOM70, which

We still know very little about how the human immune system responds to SARS-CoV-2. Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We find that all these patients had IgG and IgM antibodies that specifically bind SARS-CoV-2 proteins, particularly the N protein and S1 protein. Besides these proteins, significant antibody responses to ORF9b and NSP5 are also identified. We show that the S1 specific IgG signal positively correlates with age and the level of lactate dehydrogenase (LDH) and negatively correlates with lymphocyte percentage. Overall, this study presents a systemic view of the SARS-CoV-2 specific IgG and IgM responses and provides insights to aid the development of effective diagnostic, therapeutic and vaccination strategies.

Significance: Arsenic holds promise for treating a wide range of tumors. To understand arsenic's antitumor mechanism further, we identified 360 arsenic-binding proteins using a human proteome microarray and found proteins of glycolysis to be highly enriched. In-depth in vitro and in vivo analysis revealed that glycolysis in general and the rate-limiting enzyme hexokinase-2 of the glycolytic pathway in particular play a key role in mediating the anticancer activity of arsenic. These findings shed light on the mode of action of arsenic, and the newly identified arsenic-binding proteins may serve as a rich resource for future studies.