Despite the discovery of animal coronaviruses related to SARS-CoV-2, the evolutionary origins of this virus are elusive. We describe a meta-transcriptomic study of 411 bat samples collected from a ...small geographical region in Yunnan province, China, between May 2019 and November 2020. We identified 24 full-length coronavirus genomes, including four novel SARS-CoV-2-related and three SARS-CoV-related viruses. Rhinolophus pusillus virus RpYN06 was the closest relative of SARS-CoV-2 in most of the genome, although it possessed a more divergent spike gene. The other three SARS-CoV-2-related coronaviruses carried a genetically distinct spike gene that could weakly bind to the hACE2 receptor in vitro. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species, with the largest contiguous hotspots extending from South Laos and Vietnam to southern China. Our study highlights the remarkable diversity of bat coronaviruses at the local scale, including close relatives of both SARS-CoV-2 and SARS-CoV.
Display omitted
•Four novel SARS-CoV-2-related viruses were identified in rhinolophid bats•RpYN06 is the closest relative of SARS-CoV-2 in most of the virus genome•A high diversity of bat coronaviruses was present in a very small geographic area•Ecological modeling reveals a broad range of rhinolophid bats in parts of Asia
A study of 411 bat samples collected in Yunnan province, China between 2019 and 2020 yields 24 full-length coronavirus genomes, including four viruses highly related to SARS-CoV-2 and three to SARS. The closest relative to SARS-CoV-2 infects a species of bats that is found in regions that extend from South Laos and Vietnam to southern China.
The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein ...in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
Radiation damage to the steel material of reactor pressure vessels is a major threat to the nuclear reactor safety. It is caused by the metal atom cascade collision, initialized when the atoms are ...struck by a high-energy neutron. The paper presents MISA-MD, a new implementation of molecular dynamics, to simulate such cascade collision with EAM potential. MISA-MD realizes (1) a hash-based data structure to efficiently store an atom and find its neighbors, and (2) several acceleration and optimization strategies based on SW26010 processor of Sunway Taihulight supercomputer, including an efficient potential table storage and interpolation method, a coloring method to avoid write conflicts, and double-buffer and data reuse strategies. The experimental results demonstrated that MISA-MD has good accuracy and scalability, and obtains a parallel efficiency of over 79% in an 655-billion-atom system. Compared with a state-of-the-art MD program LAMMPS, MISA-MD requires less memory usage and achieves better computational performance.
Program Title: MISA-MD
CPC Library link to program files:https://doi.org/10.17632/x2bmx6whcd.1
Code Ocean capsule:https://doi.org/10.24433/CO.4041607.v1
Licensing provisions: BSD 3-clause
Programming language: C and C++
Nature of problem: Molecular dynamics (MD) is a significant method to simulate the cascade collision progress of the key material in nuclear reactors. However, there are many difficulties for existing MD programs to perform large scale cascade collision simulations. Thus, it is especially essential to develop a new MD software to extend cascade collision simulations to larger spatial scale and longer temporal scale.
Solution method: To achieve accuracy and effective MD cascade collision simulation, the EAM potential is selected to calculate interactional force between atoms in the simulation system. To extend MD simulation to larger scale, we proposed a hash-based data structure/algorithm to efficiently store an atom and find its neighbors, and several acceleration and optimization strategies based on SW26010 processor of Sunway Taihulight supercomputer.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide range of hosts, including hippopotami, which are semi-aquatic mammals and phylogenetically closely related to Cetacea. In this ...study, we characterized the binding properties of hippopotamus angiotensin-converting enzyme 2 (hiACE2) to the spike (S) protein receptor binding domains (RBDs) of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs). Furthermore, the cryo-electron microscopy (cryo-EM) structure of the SARS-CoV-2 PT S protein complexed with hiACE2 was resolved. Structural and mutational analyses revealed that L30 and F83, which are specific to hiACE2, played a crucial role in the hiACE2/SARS-CoV-2 RBD interaction. In addition, comparative and structural analysis of ACE2 orthologs suggested that the cetaceans may have the potential to be infected by SARS-CoV-2. These results provide crucial molecular insights into the susceptibility of hippopotami to SARS-CoV-2 and suggest the potential risk of SARS-CoV-2 VOCs spillover and the necessity for surveillance.
The hippopotami are the first semi-aquatic artiodactyl mammals wherein SARS-CoV-2 infection has been reported. Exploration of the invasion mechanism of SARS-CoV-2 will provide important information for the surveillance of SARS-CoV-2 in hippopotami, as well as other semi-aquatic mammals and cetaceans. Here, we found that hippopotamus ACE2 (hiACE2) could efficiently bind to the RBDs of the SARS-CoV-2 prototype (PT) and variants of concern (VOCs) and facilitate the transduction of SARS-CoV-2 PT and VOCs pseudoviruses into hiACE2-expressing cells. The cryo-EM structure of the SARS-CoV-2 PT S protein complexed with hiACE2 elucidated a few critical residues in the RBD/hiACE2 interface, especially L30 and F83 of hiACE2 which are unique to hiACE2 and contributed to the decreased binding affinity to PT RBD compared to human ACE2. Our work provides insight into cross-species transmission and highlights the necessity for monitoring host jumps and spillover events on SARS-CoV-2 in semi-aquatic/aquatic mammals.
Currently, monoclonal antibodies (MAbs) targeting the SARS-CoV-2 receptor binding domain (RBD) of spike (S) protein are classified into seven classes based on their binding epitopes. However, most of ...these antibodies are seriously impaired by SARS-CoV-2 Omicron and its subvariants, especially the recent BQ.1.1, XBB and its derivatives. Identification of broadly neutralizing MAbs against currently circulating variants is imperative. In this study, we identified a "breathing" cryptic epitope in the S protein, named as RBD-8. Two human MAbs, BIOLS56 and IMCAS74, were isolated recognizing this epitope with broad neutralization abilities against tested sarbecoviruses, including SARS-CoV, pangolin-origin coronaviruses, and all the SARS-CoV-2 variants tested (Omicron BA.4/BA.5, BQ.1.1, and XBB subvariants). Searching through the literature, some more RBD-8 MAbs were defined. More importantly, BIOLS56 rescues the immune-evaded antibody, RBD-5 MAb IMCAS-L4.65, by making a bispecific MAb, to neutralize BQ.1 and BQ.1.1, thereby producing an MAb to cover all the currently circulating Omicron subvariants. Structural analysis reveals that the neutralization effect of RBD-8 antibodies depends on the extent of epitope exposure, which is affected by the angle of antibody binding and the number of up-RBDs induced by angiotensin-converting enzyme 2 binding. This cryptic epitope which recognizes non- receptor binding motif (non-RBM) provides guidance for the development of universal therapeutic antibodies and vaccines against COVID-19.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has an extremely broad host range that includes hippopotami, which are phylogenetically closely related to whales. The cellular ...ACE2 receptor is one of the key determinants of the host range. Here, we found that ACE2s from several marine mammals and hippopotami could efficiently bind to the receptor-binding domain (RBD) of both SARS-CoV and SARS-CoV-2 and facilitate the transduction of SARS-CoV and SARS-CoV-2 pseudoviruses into ACE2-expressing cells. We further resolved the cryo-electron microscopy complex structures of the minke whale ACE2 and sea lion ACE2, respectively, bound to the RBDs, revealing that they have similar binding modes to human ACE2 when it comes to the SARS-CoV-2 RBD and SARS-CoV RBD. Our results indicate that marine mammals could potentially be new victims or virus carriers of SARS-CoV-2, which deserves further careful investigation and study. It will provide an early warning for the prospective monitoring of marine mammals.
Following the outbreak of coronavirus disease 2019 (COVID-19), several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related coronaviruses have been discovered. Previous research has ...identified a novel lineage of SARS-CoV-2-related CoVs in bats, including RsYN04, which recognizes human angiotensin-converting enzyme 2 (ACE2) and thus poses a potential threat to humans. Here, we screened the binding of the RsYN04 receptor-binding domain (RBD) to ACE2 orthologs from 52 animal species and found that the virus showed a narrower ACE2-binding spectrum than SARS-CoV-2. However, the presence of the T484W mutation in the RsYN04 RBD broadened its range. We also evaluated 44 SARS-CoV-2 antibodies targeting seven epitope communities in the SARS-CoV-2 RBD, together with serum obtained from COVID-19 convalescents and vaccinees, to determine their cross-reaction against RsYN04. Results showed that no antibodies, except for the RBD-6 and RBD-7 classes, bound to the RsYN04 RBD, indicating substantial immune differences from SARS-CoV-2. Furthermore, the structure of the RsYN04 RBD in complex with cross-reactive antibody S43 in RBD-7 revealed a potently broad epitope for the development of therapeutics and vaccines. Our findings suggest RsYN04 and other viruses belonging to the same clade have the potential to infect several species, including humans, highlighting the necessity for viral surveillance and development of broad anti-coronavirus countermeasures.
Radiation damage to the steel material of reactor pressure vessels is a major threat to the nuclear reactor safety. It is caused by the metal atom cascade collision, initialized when the atoms are ...struck by a high-energy neutron. The paper presents MISA-MD, a new implementation of molecular dynamics, to simulate such cascade collision with EAM potential. MISA-MD realizes (1) a hash-based data structure to efficiently store an atom and find its neighbors, and (2) several acceleration and optimization strategies based on SW26010 processor of Sunway Taihulight supercomputer, including an efficient potential table storage and interpolation method, a coloring method to avoid write conflicts, and double-buffer and data reuse strategies. The experimental results demonstrated that MISA-MD has good accuracy and scalability, and obtains a parallel efficiency of over 79% in an 655-billion-atom system. Compared with a state-of-the-art MD program LAMMPS, MISA-MD requires less memory usage and achieves better computational performance.
Different soils have large differences in efficiencies and mechanisms in arsenic (As) adsorption, due to the dissimilarities of soil minerals, organic matter (OM) and physiochemical properties. To ...understand the differences of As adsorption resulting from these differences among soils, the red soil weathered from granite (RS-G) and sandstone (RS-S) were employed to comparatively study the minerals, OM, physicochemical properties, and the isotherms and kinetics of As(V) adsorption. The soil samples were collected at 0–20 cm depth on the top of the mother rocks in Dingziwan and Yuelu Mountain, Changsha, Hunan province in China. The soil minerals were characterized by X-ray powder diffraction (XRD). The specific surface area (SSA) of the soil samples was determined using a BET Analyzer with nitrogen and multi-point analysis after degassing overnight at 100 °C. The cation exchange capacity (CEC) was determined by the method of ammonium acetate centrifugal exchange, and the OM, pH, and point of zero charge (pH
PZC
) were measured using improved potassium dichromate volumetric weight method, titration, and potentiometric titration method, respectively. The As(V) in the solution was measured by graphite furnace atomic absorption spectrometry (GFAAS). RS-G contains more clay minerals and iron (hydr)oxides, and less quartz than RS-S by 25.31%, 111.69%, and − 22.39%, respectively. There are similar SSA, CEC, and OM content, but different pH
pzc
and OM sources between the two soil types. The adsorption experiments reveal (1) the As(V) removal efficiency drops rapidly as the initial As(V) concentration is greater than 4.0 mg/L for RS-G and 8.0 mg/L for RS-S, and that of RS-S decreases more slowly as the As(V) concentration increasing from 4.0 to 20.0 mg/L, (2) the As(V) removal efficiency decreases rapidly as the pH is larger than 8.0 for RS-G and 7.0 for RS-S, and (3) the time reaching equilibrium is 120 min for RS-G and 180 min for RS-S, and their kinetics show two and three stages adsorption processes, respectively. The higher mineral content and pH
PZC
are the main causes for RS-G showing higher As(V) removal efficiency, shorter time to reach equilibrium, and wider pH range for As(V) adsorption. The young OM in RS-G may be responsible for the rapid decrease of As(V) removal efficiency as the As(V) concentration larger than 4.0 mg/L. Comparatively, the RS-G is more efficient for As(V) adsorption, and is more potential for groundwater protection from As contamination.
PDF
