Westlake University

About: Westlake University is a education organization based out in Hangzhou, China. It is known for research contribution in the topics: Chemistry & Computer science. The organization has 1023 authors who have published 1497 publications receiving 20050 citations. The organization is also known as: Westlake Institute for Advanced Study, Zhejiang.

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2.

Abstract: Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.

A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2.

Abstract: Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients Three mAbs showed neutralizing activities against authentic SARS-CoV-2 One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 31 angstroms and local resolution of 33 angstroms for the 4A8-NTD interface This points to the NTD as a promising target for therapeutic mAbs against COVID-19

Genetic mechanisms of critical illness in Covid-19.

Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Advances and issues in developing salt-concentrated battery electrolytes

Abstract: With a worldwide trend towards the efficient use of renewable energies and the rapid expansion of the electric vehicle market, the importance of rechargeable battery technologies, particularly lithium-ion batteries, has steadily increased. In the past few years, a major breakthrough in electrolyte materials was achieved by simply increasing the salt concentration in suitable salt–solvent combinations, offering technical superiority in numerous figures of merit over alternative materials. This long-awaited, extremely simple yet effective strategy can overcome most of the remaining hurdles limiting the present lithium-ion batteries without sacrificing manufacturing efficiency, and hence its impact is now widely felt in the scientific community, with serious potential for industrial development. This Review aims to provide timely and objective information that will be valuable for designing better realistic batteries, including a multi-angle analysis of their advantages and disadvantages together with future perspectives. Emphasis is placed on the pathways to address the remaining technical and scientific issues rather than re-highlighting the many technical advantages. New electrolyte materials can offer breakthroughs in the development of next-generation batteries. Here Atsuo Yamada and colleagues review the progress made and the road ahead for salt-concentrated electrolytes, an emerging and promising electrolyte candidate.