Critical ace2 determinants of sars-cov-2 and group 2b coronavirus infection and replication

The angiotensin-converting enzyme 2 (ACE2) receptor is a major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host range determinant, and understanding SARS-CoV-2-ACE2 interactions will provide important insights into COVID-19 pathogenesis and animal model development. SARS-CoV-2 cannot infect mice due to incompatibility between its receptor binding domain and the murine ACE2 receptor. Through molecular modeling and empirical in vitro validation, we identified 5 key amino acid differences between murine and human ACE2 that mediate SARS-CoV-2 infection, generating a chimeric humanized murine ACE2. Additionally, we examined the ability of the humanized murine ACE2 receptor to permit infection by an additional preemergent group 2B coronavirus, WIV-1, providing evidence for the potential pan-virus capabilities of this chimeric receptor. Finally, we predicted the ability of these determinants to inform host range identification of preemergent coronaviruses by evaluating hot spot contacts between SARS-CoV-2 and additional potential host receptors. Our results identify residue determinants that mediate coronavirus receptor usage and host range for application in SARS-CoV-2 and emerging coronavirus animal model development. IMPORTANCE SARS-CoV-2 (the causative agent of COVID-19) is a major public health threat and one of two related coronaviruses that have caused epidemics in modern history. A method of screening potential infectible hosts for preemergent and future emergent coronaviruses would aid in mounting rapid response and intervention strategies during future emergence events. Here, we evaluated determinants of SARS-CoV-2 receptor interactions, identifying key changes that enable or prevent infection. The analysis detailed in this study will aid in the development of model systems to screen emergent coronaviruses as well as treatments to counteract infections

Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses

Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. Methods: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. Findings: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. Interpretation: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. Funding: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF

Probing Lorentz and CPT violation with space-based experiments

Space-based experiments offer sensitivity to numerous unmeasured effects involving Lorentz and CPT violation. We provide a classification of clock sensitivities and present explicit expressions for time variations arising in such experiments from nonzero coefficients in the Lorentz- and CPT-violating Standard-Model Extension.Comment: 15 page

Moments of the Hadronic Invariant Mass Spectrum in B --> X_c l nu Decays at Belle

We present a measurement of the hadronic invariant mass squared (M^2_X) spectrum in charmed semileptonic B meson decays B --> X_c l nu based on 140 fb^-1 of Belle data collected near the Y(4S) resonance. We determine the first, the second central and the second non-central moments of this spectrum for lepton energy thresholds ranging between 0.7 and 1.9 GeV. Full correlations between these measurements are evaluated.Comment: published version of the paper (one figure added, minor changes in the text); 16 pages, 3 figures, 10 table

Lorentz and CPT Violation in Neutrinos

A general formalism is presented for violations of Lorentz and CPT symmetry in the neutrino sector. The effective hamiltonian for neutrino propagation in the presence of Lorentz and CPT violation is derived, and its properties are studied. Possible definitive signals in existing and future neutrino-oscillation experiments are discussed. Among the predictions are direction-dependent effects, including neutrino-antineutrino mixing, sidereal and annual variations, and compass asymmetries. Other consequences of Lorentz and CPT violation involve unconventional energy dependences in oscillation lengths and mixing angles. A variety of simple models both with and without neutrino masses are developed to illustrate key physical effects. The attainable sensitivities to coefficients for Lorentz violation in the Standard-Model Extension are estimated for various types of experiments. Many experiments have potential sensitivity to Planck-suppressed effects, comparable to the best tests in other sectors. The lack of existing experimental constraints, the wide range of available coefficient space, and the variety of novel effects imply that some or perhaps even all of the existing data on neutrino oscillations might be due to Lorentz and CPT violation.Comment: 25 pages REVTe

Precise measurement of hadronic tau-decays with an eta meson

We have studied hadronic tau decay modes involving an eta meson using 490 fb^{-1} of data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The following branching fractions have been measured: B(tau- -> K- eta nu)=(1.58 +- 0.05 +- 0.09)x 10^{-4}, B(tau- -> K- pi0 eta nu)=(4.6 +- 1.1 +- 0.4)x 10^{-5}, B(tau- -> pi- pi0 eta nu)=(1.35 +- 0.03 +- 0.07)x 10^{-3}, B(tau- -> pi- KS eta nu)=(4.4 +- 0.7 +- 0.2)x 10^{-5}, and B(tau- -> K^{*-} eta nu)=(1.34 +- 0.12 +- 0.09)x 10^{-4}. These results are substantially more precise than previous measurements. The new measurements are compared with theoretical calculations based on the CVC hypothesis or the chiral perturbation theory. We also set upper limits on branching fractions for tau decays into K- KS eta nu, pi- KS pi0 eta nu, K- eta eta nu, pi- eta eta nu and non-resonant K- pi^0 eta nu final states.Comment: 24 pages, 7 figure

Measurements of exclusive B_s^0 decays at the Y(5S) resonance

Several exclusive $B_s^0$ decays are studied using a 1.86 fb-1 data sample collected at the Y(5S) resonance with the Belle detector at the KEKB asymmetric energy e^+ e^- collider. In the $B_s^0 \to D_s^- \pi^+$ decay mode we find 10 $B_s^0$ candidates and measure the corresponding branching fraction. Combining the B_s^0 -> D_s^{(*)-} \pi^+, B_s^0 -> D_s^{(*)-} \rho^+, B_s^0 -> J/\psi \phi and B_s^0 -> J/\psi \eta decay modes, a significant $B_s^0$ signal is observed. The ratio \sigma (e^+ e^- -> B_s^* \bar{B}_s^*) / \sigma (e^+ e^- -> B_s^{(*)} \bar{B}_s^{(*)}) = (93^{+7}_{-9} \pm 1)% is obtained at the Y(5S) energy, indicating that $B_s^0$ meson production proceeds predominantly through the creation of $B^*_s \bar{B}^*_s$ pairs. The $B_s^0$ and $B_s^*$ meson masses are measured to be M(B_s^0)=(5370 \pm 1 \pm 3)MeV/c^2 and M(B_s^*)=(5418 \pm 1 \pm 3)MeV/c^2. Upper limits on the B_s^0 -> \gamma \gamma, B_s^0 -> \phi \gamma, B_s^0 -> K^+ K^- and B_s^0 -> D_s^{(*)+} D_s^{(*)-} branching fractions are also reported.Comment: 9 pages, 5 figures, published in Phys. Rev. D76, 012002 (2007

Measurement of the near-threshold e+e−→DDˉe^+e^- \to D \bar D cross section using initial-state radiation

We report measurements of the exclusive cross section for $e^+e^- \to D \bar D$, where $D=D^0$ or $D^+$, in the center-of-mass energy range from the $D \bar D$ threshold to $5\mathrm{GeV}/c^2$ with initial-state radiation. The analysis is based on a data sample collected with the Belle detector with an integrated luminosity of 673 $\mathrm{fb}^{-1}$.Comment: Presented at EPS07 and LP07 conferences, published in PRD(RC

Search for Resonant B±→K±h→K±γγB^{\pm}\to K^{\pm} h \to K^{\pm} \gamma \gamma Decays at Belle

We report measurements and searches for resonant $B^{\pm} \to K^{\pm} h \to K^{\pm} \gamma \gamma$ decays where $h$ is a $\eta,\eta^{\prime},\eta_{c},\eta_{c}(2S),\chi_{c0},\chi_{c2},J/\psi$ meson or the X(3872) particle.Comment: accepted by Physics Letters

Search for B+ -> D*+ pi0 decay

We report on a search for the doubly Cabibbo suppressed decay B+ -> D*+ pi0, based on a data sample of 657 million BBbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric energy e+ e- collider. We find no significant signal and set an upper limit of Br(B+ -> D*+ pi0) < 3.6 x 10^-6 at the 90% confidence level. This limit can be used to constrain the ratio between suppressed and favored B -> D* pi decay amplitudes, r < 0.051, at the 90% confidence level.Comment: 5pages, 2figures, submitted to PRL (v1); PRL published version (v2: minor corrections in the text