Ten measures of experimental electron-density-map quality are examined and the skewness of electron density is found to be the best indicator of actual map quality. A Bayesian approach to estimating map quality is developed and used in the PHENIX AutoSol wizard to make decisions during automated structure solution.

Decision-making in structure solution using Bayesian estimates of map quality: the PHENIX autosol wizard

http://www.cell.com/article/S0092867422000010/pdf

Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2

http://www.cell.com/article/S0092867422000770/pdf

Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats1–4, including the closest virus from R. affinis, RaTG13 (refs. 5,6), and pangolins7–9. SARS-CoV-2 has a mosaic genome, to which different progenitors contribute. The spike sequence determines the binding affinity and accessibility of its receptor-binding domain to the cellular angiotensin-converting enzyme 2 (ACE2) receptor and is responsible for host range10–12. SARS-CoV-2 progenitor bat viruses genetically close to SARS-CoV-2 and able to enter human cells through a human ACE2 (hACE2) pathway have not yet been identified, although they would be key in understanding the origin of the epidemic. Here we show that such viruses circulate in cave bats living in the limestone karstic terrain in northern Laos, in the Indochinese peninsula. We found that the receptor-binding domains of these viruses differ from that of SARS-CoV-2 by only one or two residues at the interface with ACE2, bind more efficiently to the hACE2 protein than that of the SARS-CoV-2 strain isolated in Wuhan from early human cases, and mediate hACE2-dependent entry and replication in human cells, which is inhibited by antibodies that neutralize SARS-CoV-2. None of these bat viruses contains a furin cleavage site in the spike protein. Our findings therefore indicate that bat-borne SARS-CoV-2-like viruses that are potentially infectious for humans circulate in Rhinolophus spp. in the Indochinese peninsula. A study reports the detection and characterization of SARS-CoV-2-like viruses in Laotian cave-dwelling bats that are also demonstrated to infect human cells through the ACE2 pathway. 

/pdf/bat-coronaviruses-related-to-sars-cov-2-and-infectious-for-2jxx1vkb.pdf

Bat coronaviruses related to SARS-CoV-2 and infectious for human cells

Abstract Two different sarbecoviruses have caused major human outbreaks in the past two decades 1,2 . Both of these sarbecoviruses, SARS-CoV-1 and SARS-CoV-2, engage ACE2 through the spike receptor-binding domain 2–6 . However, binding to ACE2 orthologues of humans, bats and other species has been observed only sporadically among the broader diversity of bat sarbecoviruses 7–11 . Here we use high-throughput assays 12 to trace the evolutionary history of ACE2 binding across a diverse range of sarbecoviruses and ACE2 orthologues. We find that ACE2 binding is an ancestral trait of sarbecovirus receptor-binding domains that has subsequently been lost in some clades. Furthermore, we reveal that bat sarbecoviruses from outside Asia can bind to ACE2. Moreover, ACE2 binding is highly evolvable—for many sarbecovirus receptor-binding domains, there are single amino-acid mutations that enable binding to new ACE2 orthologues. However, the effects of individual mutations can differ considerably between viruses, as shown by the N501Y mutation, which enhances the human ACE2-binding affinity of several SARS-CoV-2 variants of concern 12 but substantially decreases it for SARS-CoV-1. Our results point to the deep ancestral origin and evolutionary plasticity of ACE2 binding, broadening the range of sarbecoviruses that should be considered to have spillover potential. 

/pdf/ace2-binding-is-an-ancestral-and-evolvable-trait-of-st26s3bv.pdf

ACE2 binding is an ancestral and evolvable trait of sarbecoviruses

Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species.

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly fatal hemorrhagic disease of pigs, which has resulted in great economic losses to the global pork industry, especially in Asia. ASFV particles are comprised of multiple layers encompassing the genomic DNA. Though the capsid structure has been determined, very little is known about the structure of the core shell. The precursor polyprotein pp62 is the structural component of the core shell that gives rise to the p35 and p15 proteins. Herein, we describe the crystal structure of p15 at a resolution of 2.2 A. The structure of p15 exhibits as a trimeric conformation that is mainly mediated by intermolecular disulfide bonds and supported by multiple hydrogen bond interactions. The button conformation on the surface of adjacent molecules may also play a role in trimeric formation of the ASFV p15. The center of the p15 trimer exhibits opposite electrostatic characteristics on each side. These findings benefit our understanding of ASFV core shell assembly and will aid in the design of antiviral drugs and vaccines.

Linjie Li

Papers

Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species.

Crystal structure of the African swine fever virus core shell protein p15