A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world 1-3 . Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor 4 . Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses 1-3,5 . The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.The emergence of the highly pathogenic coronavirus SARS-CoV-2 in Wuhan and its rapid international spread has posed a serious global public-health emergency 1-3 . Similar to individuals who were infected by pathogenic SARS-CoV in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, patients infected by SARS-CoV-2 showed a range of symptoms including dry cough, fever, headache, dyspnoea and pneumonia with an estimated mortality rate ranging from 3 to 5% 6-8 . Since the initial outbreak in December of 2019, SARS-CoV-2 has spread throughout China and to more than 80 other countries and areas worldwide. As of 5 March 2020, 80,565 cases in China have been confirmed with the infection and 3,015 infected patients have died (https://www.who.int/emergencies/ diseases/novel-coronavirus-2019/situation-reports/). As a result, the epicentre Wuhan and the neighbouring cities have been under lockdown to minimize the continued spread and the WHO (World Health Organization) has announced a Public Health Emergency of International Concern owing to the rapid and global dissemination of SARS-CoV-2.Phylogenetic analyses of the coronavirus genomes have revealed that SARS-CoV-2 is a member of the Betacoronavirus genus, which includes SARS-CoV, MERS-CoV, bat SARS-related coronaviruses (SARSr-CoV), as well as others identified in humans and diverse animal species [1][2][3]5 . Bat coronavirus RaTG13 appears to be the closest relative of the SARS-CoV-2, sharing more than 93.1% sequence identity in the spike (S) gene. SARS-CoV and other SARSr-CoVs, however, are distinct from SARS-CoV-2 and share less than 80% sequence identity 1 .Coronaviruses use the homotrimeric spike glycoprotein (comprising a S1 subunit and S2 subunit in each spike monomer) on the envelope to ...

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global health emergency that is in urgent need of intervention 1-3. The entry of SARS-CoV-2 into its target cells depends on binding between the receptor-binding domain (RBD) of the viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2) 2,4-6. Here we report the isolation and characterization of 206 RBD-specific monoclonal antibodies derived from single B cells from 8 individuals infected with SARS-CoV-2. We identified antibodies that potently neutralize SARS-CoV-2; this activity correlates with competition with ACE2 for binding to RBD. Unexpectedly, the anti-SARS-CoV-2 antibodies and the infected plasma did not cross-react with the RBDs of SARS-CoV or Middle East respiratory syndrome-related coronavirus (MERS-CoV), although there was substantial plasma cross-reactivity to their trimeric spike proteins. Analysis of the crystal structure of RBD-bound antibody revealed that steric hindrance inhibits viral engagement with ACE2, thereby blocking viral entry. These findings suggest that anti-RBD antibodies are largely viral-species-specific inhibitors. The antibodies identified here may be candidates for development of clinical interventions against SARS-CoV-2. The rapid international transmission of SARS-CoV-2 poses a serious global health emergency with no available treatments or vaccine 1-3. SARS-CoV-2 shares substantial genetic and functional similarity with other human betacoronaviruses, including SARS-CoV and MERS-CoV 2,4-8. SARS-CoV-2 uses an envelope homotrimeric spike glycoprotein to interact with the cellular receptor ACE2 2,5,6,8. Binding with ACE2 triggers a cell membrane fusion cascade that results in viral entry. This suggests that disruption of the RBD-ACE2 interaction would block SARS-CoV-2 cell entry. The high-resolution structure of SARS-CoV-2 RBD bound to the N-terminal peptidase domain of ACE2 has recently been determined 6-8. The ACE2-binding mechanism is nearly identical between SARS-CoV-2 and SARS-CoV RBDs 7-10. Animal studies on RBD-based vaccines against SARS-CoV and MERS-CoV have shown strong polyclonal antibody responses that inhibit viral entry 11,12. These findings suggest that anti-RBD antibodies should effectively block SARS-CoV-2 entry. In this study, we report on RBD-specific monoclonal antibodies obtained from individuals infected with SARS-CoV-2. Plasma antibody response against SARS-CoV-2 We collected cross-sectional and longitudinal blood samples from eight patients infected with SARS-CoV-2, who were infected during the early outbreak in Shenzhen (Supplementary Table 1). Samples were named according to patient ID and A, B, or C depending on when they were collected. Six patients (P1 to P4, P8 and P16) had recently travelled to Wuhan and the others (P5 and P22) had direct contact with people who had recently been in Wuhan. P1 to P5 comprise a family cluster, including the first documented case of human-to-human transmission...

3D printing and numerical analysis are combined to design a new class of architected materials that contain bistable beam elements and exhibit controlled trapping of elastic energy. The proposed energy-absorbing structures are reusable. Moreover, the mechanism of energy absorption stems solely from the structural geometry of the printed beam elements, and is therefore both material- and loading-rate independent.

We report a new class of tunable and switchable acoustic metamaterials comprising resonating units dispersed into an elastic matrix. Each resonator consists of a metallic core connected to the elastomeric matrix through elastic beams, whose buckling is intentionally exploited as a novel and effective approach to control the propagation of elastic waves. We first use numerical analysis to show the evolution of the locally resonant band gap, fully accounting for the effect of nonlinear pre-deformation. Then, we experimentally measure the transmission of vibrations as a function of the applied loading in a finite-size sample and find excellent agreement with our numerical predictions. The proposed concept expands the ability of existing acoustic metamaterials by enabling tunability over a wide range of frequencies. Furthermore, we demonstrate that in our system the deformation can be exploited to turn on or off the band gap, opening avenues for the design of adaptive switches.

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