Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes. (preprint)

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed and open. The locked conformations feature tightly packed trimers with structural elements incompatible with RBD in "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably due to their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. Intriguingly, locked conformations were the only conformations captured for S proteins of bat and pangolin origin SARS-related coronaviruses. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures to other available spike structures of Sarbecoviruses to identify conserved features and discuss their possible functions.

The Partisan Mask: Political Orientation, Collectivism, and Religiosity Predict Mask Use During COVID-19 (preprint)

In the United States, the COVID-19 pandemic became an unconventional vehicle to advance partisan rhetoric and antagonism. Using data available at the individual- (Study 1; N = 4,220), county- (Study 2; n = 3,046), and state-level (n = 49), we found that partisanship and political orientation was a robust and strong correlate of mask use. Political conservatism and Republican partisanship were related to downplaying the severity of COVID-19 and perceiving masks as being ineffective that, in turn, were related to lower mask use. In contrast, we found that counties with majority Democrat partisanship reported greater mask use, controlling for various socioeconomic and demographic factors. Lastly, states with strong cultural collectivism reported greater mask use while those with strong religiosity reported the opposite. States with greater Democrat partisanship and strong cultural collectivism subsequently reported lower COVID-19 deaths, mediated by greater mask use and lower COVID-19 cases, in the five months following the second wave of COVID-19 in the US during the Summer of 2020. Nonetheless, more than the majority for Democrats (91.58%), Republicans (77.52%), and third-party members (82.48%) reported using masks. Implications for findings are discussed.

The Architecture of Inactivated SARS-CoV-2 with Postfusion Spikes Revealed by CryoEM and CryoET (preprint)

The outbreak of SARS-CoV-2 in December 2019, led to the ongoing global pandemic of coronavirus disease 2019 (COVID‑19), which has claimed more than a half million lives in a few months. Enormous efforts are being made in developing vaccines and therapeutic treatment to fight against COVID-19. Inactivated SARS-CoV-2 viruses are currently used as vaccine candidates; therefore, it is important to understand the architecture of SARS-CoV-2. We have propagated and purified a clinical strain of SARS-CoV-2 and genetically and structurally characterized β-propiolactone inactivated viruses. We observed that the virus particles are roughly spherical or moderately pleiomorphic. Although a small fraction of prefusion spikes are observed, the majority of viral spikes appear nail-shaped resembling a postfusion state, where S1 protein of the spike has disassociated. Cryo-electron tomography and subtomogram averaging of these spikes yielded a density map which closely matches the overall structure of SARS-CoV S2 spike and their corresponding glycosylation sites. Our findings have major implications in SARS-CoV-2 vaccine design owing to the critical importance of prefusion immunogens.Funding: This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality(202002073000002), the National Institutes of Health grant P50AI150481 (P.Z.), the UK Wellcome Trust Investigator Award 206422/Z/17/Z(P.Z.), and the UK Biotechnology and Biological Sciences Research Council grant BB/S003339/1 (P.Z.). Conflict of Interest: The authors declare no competing financial or non-financial interests. Ethical Approval: The research received approval from the Research Ethics Committee of Shenzhen Third People's Hospital, China (approval number: 2020-038). The Research Ethics Committee waived the requirement informed consent before the study started because of the urgent need to collect epidemiological and clinical data. We analyzed the data anonymously.

An Early Examination: Psychological, Health, and Economic Correlates and Determinants of Social Distancing Amidst COVID-19 (preprint)

With the exponential spread of COVID-19 across the United States, federal and local government agencies have issued orders for residents to shelter-in-place. This study utilizes data collected from Unacast Inc. spanning observations of 3,142 counties across 50 states and the District of Columbia (N = 230,846) from March 8, 2020 to April 13, 2020 (n = 104,930) and from April 14, 2020 to May 24, 2020 (n = 131,912) in a 3-level multilevel model to examine the correlates of social distancing behavior, as measured by the relative reduction in 1) distance traveled and 2) non-essential visitations since baseline pre-COVID-19 times. Results indicate that educational attainment and political partisanship were the most consistent correlates of social distancing. State-level indicators of culture appeared to have differentiated effects depending on whether the model outcomes were reduction in general mobility or to non-essential venues. State-level neuroticism was generally positively related to social distancing, but states marked by high neuroticism were slower to engage in such behaviors. Counties and states characterized as already engaging in preventive health measures (e.g., vaccination rates, preparedness for at-risk populations) enjoyed quicker engagement in social distancing. Specific implications of findings and future directions are discussed.

Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM (preprint)

Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.