The emergence of SARS-CoV-2 infection has posed unprecedented threat to global public health. The virus-encoded non-structural protein 14 (nsp14) is a bi-functional enzyme consisting of an exoribonuclease (ExoN) domain and a methyltransferase (MTase) domain and plays a pivotal role in viral replication. Here, we report the structure of SARS-CoV-2 nsp14-ExoN domain bound to its co-factor nsp10 and show that, compared to the SARS-CoV nsp10/nsp14-full-length complex, SARS-CoV-2 nsp14-ExoN retains an integral exoribonuclease fold and preserves an active configuration in the catalytic center. Analysis of the nsp10/nsp14-ExoN interface reveals a footprint in nsp10 extensively overlapping with that observed in the nsp10/nsp16 structure. A marked difference in the co-factor when engaging nsp14 and nsp16 lies in helix-α1′, which is further experimentally ascertained to be involved in nsp14-binding but not in nsp16-engagement. Finally, we also show that nsp10/nsp14-ExoN is enzymatically active despite the absence of nsp14-MTase domain. These data demonstrate that SARS-CoV-2 nsp10/nsp14-ExoN functions as an exoribonuclease with both structural and functional integrity.
Highlights d RABV-G ecto-domain protein structure is revealed using a fusion-loop substitution strategy d Crystal structures of RABV-G at both basic and acidic pHs are solved d Structural comparison reveals basis of pH-dependent structural transitions in RABV-G d Complex structure shows 523-11 antibody binds a bipartite epitope for neutralization
Background: COVID-19 has become one of the most serious global epidemics in the 21st Century. This study aims to explore the distribution of research capabilities of countries, institutions, and researchers, and the hotspots and frontiers of coronavirus research in the past two decades. In it, references for funding support of urgent projects and international cooperation among research institutions are provided. Method: the Web of Science core collection database was used to retrieve the documents related to coronavirus published from 2003 to 2020. Citespace.5.6.R2, VOSviewer1.6.12, and Excel 2016 were used for bibliometric analysis. Results: 11,036 documents were retrieved, of which China and the United States have contributed the most coronavirus studies, Hong Kong University being the top contributor. Regarding journals, the Journal of Virology has contributed the most, while in terms of researchers, Yuen Kwok Yung has made the most contributions. The proportion of documents published by international cooperation has been rising for decades. Vaccines for SARS-CoV-2 are under development, and clinical trials of several drugs are ongoing. Conclusions: international cooperation is an important way to accelerate research progress and achieve success. Developing corresponding vaccines and drugs are the current hotspots and research directions.
The Cu4I4-MOF-based mixed matrix membranes (MMMs) can be readily prepared by one-step in situ self-assembly of a tri-armed oxadiazole-bridged ligand and CuI in polymer binder solution under ambient conditions. The visual and luminescent HCl(g) sensing detecting limits of the resulting Cu4I4-MOF-based MMMs are 3.2 and 1.6 ppb, respectively, and the response time is less than 1 min.
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