The E3 Ubiquitin Ligase RNF5 Facilitates SARS-CoV-2 Membrane Protein-Mediated Virion Release.

As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains a membrane protein (M) that mediates viral release from cellular membranes. However, the molecular mechanisms of SARS-CoV-2 virion release remain poorly understood. In the present study, we performed RNA interference (RNAi) screening and identified the E3 ligase RNF5, which mediates the ubiquitination of SARS-CoV-2 M at residue K15 to enhance the interaction of the viral envelope protein (E) with M, whereas the deubiquitinating enzyme POH1 negatively regulates this process. The M-E complex ensures the uniform size of viral particles for viral maturation and mediates virion release. Moreover, M traffics from the Golgi apparatus to autophagosomes and uses autophagosomes for virion release, and this process is dependent on RNF5-mediated ubiquitin modification and M-E interaction. These results demonstrate that ubiquitin modification of SARS-CoV-2 M stabilizes the M-E complex and uses autophagosomes for virion release. IMPORTANCE Enveloped virus particles are released from the membranes of host cells, and viral membrane proteins (M) are critical for this process. A better understanding of the molecular mechanisms of SARS-CoV-2 assembly and budding is critical for the development of antiviral therapies. Envelope protein (E) and M of SARS-CoV-2 form complexes to mediate viral assembly and budding. RNF5 was identified to play a role as the E3 ligase, and POH1 was demonstrated to function as the deubiquitinating enzyme of SARS-CoV-2 M. The two components collectively regulate the interaction of M with E to promote viral assembly and budding. Ubiquitinated M uses autophagosomes for viral release. Our findings provide insights into the mechanisms of SARS-CoV-2 assembly and budding, demonstrating the importance of ubiquitination modification and autophagy in viral replication.

Experience of the COVID-19 pandemic in Wuhan leads to a lasting increase in social distancing.

On 11th Jan 2020, the first COVID-19 related death was confirmed in Wuhan, Hubei. The Chinese government responded to the outbreak with a lockdown that impacted most residents of Hubei province and lasted for almost three months. At the time, the lockdown was the strictest both within China and worldwide. Using an interactive web-based experiment conducted half a year after the lockdown with participants from 11 Chinese provinces, we investigate the behavioral effects of this 'shock' event experienced by the population of Hubei. We find that both one's place of residence and the strictness of lockdown measures in their province are robust predictors of individual social distancing behavior. Further, we observe that informational messages are effective at increasing compliance with social distancing throughout China, whereas fines for noncompliance work better within Hubei province relative to the rest of the country. We also report that residents of Hubei increase their propensity to social distance when exposed to social environments characterized by the presence of a superspreader, while the effect is not present outside of the province. Our results appear to be specific to the context of COVID-19 and are not explained by general differences in risk attitudes and social preferences.

Online prices and inflation during the nationwide COVID-19 quarantine period: Evidence from 107 Chinese websites.

Given the lack of activity in China's offline economy during the COVID-19 quarantine period, online prices provide new insights for analyzing the impacts of the pandemic on the economy. Using online prices from 107 websites in China and the DiD method to remove the Spring Festival effect, we show that the pandemic leads to a 0.4% surge in the overall inflation rate, a 20% decrease in the price change probability, and a 1% decline in the size of absolute price changes. Moreover, the pandemic had heterogeneous impacts on different sectors, leading to significant structural changes in inflation. Specifically, the pandemic hindered the price correction behavior after Spring Festival, and whether products could be consumed while customers stayed at home was an important factor affecting price adjustment and inflation dynamics.

GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.

The interval between onset and admission predicts disease progression in COVID-19 patients.

BACKGROUND: The prognostic role of the interval between disease onset and hospital admission (O-A interval) was undetermined in patients with the coronavirus disease 2019 (COVID-19). METHODS: A total of 205 laboratory-confirmed inpatients admitted to Hankou hospital of Wuhan from January 11 to March 8, 2020 were consecutively included in this retrospective observational study. Demographic data, medical history, laboratory testing results were collected from medical records. Univariate and multivariate logistic regression models were used to evaluate the prognostic effect of the O-A interval (≤7 versus >7 days) on disease progression in mild-to-moderate patients. For severe-to-critical patients, the in-hospital mortality and the length of hospital stay were compared between the O-A interval subgroups using log-rank test and Mann-Whitney U test, respectively. RESULTS: Mild-to-moderate patients with a short O-A interval (≤7 days) are more likely to deteriorate to severe-to-critical stage compared to those with a long O-A interval (>7 days) [unadjusted odds ratio =2.93, 95% confidence interval (CI), 1.32-6.55; adjusted odds ratio =3.44, 95% CI, 1.20-9.83]. No association was identified between the O-A interval and the mortality or the length of hospital stay of severe-to-critical patients. CONCLUSIONS: The O-A interval has predictive values for the disease progression in mild-to-moderate COVID-19 patients. Under circumstances of the specific health system in Wuhan, China, the spontaneous healthcare-seeking behavior is usually determined by patients' own heath conditions. Hence, the O-A interval can be reflective of the natural course of COVID-19 to some extent. However, our findings should be validated further in other cohorts and in other health systems.

Impact of temperature and relative humidity on the transmission of COVID-19: a modelling study in China and the United States.

OBJECTIVES: We aim to assess the impact of temperature and relative humidity on the transmission of COVID-19 across communities after accounting for community-level factors such as demographics, socioeconomic status and human mobility status. DESIGN: A retrospective cross-sectional regression analysis via the Fama-MacBeth procedure is adopted. SETTING: We use the data for COVID-19 daily symptom-onset cases for 100 Chinese cities and COVID-19 daily confirmed cases for 1005 US counties. PARTICIPANTS: A total of 69 498 cases in China and 740 843 cases in the USA are used for calculating the effective reproductive numbers. PRIMARY OUTCOME MEASURES: Regression analysis of the impact of temperature and relative humidity on the effective reproductive number (R value). RESULTS: Statistically significant negative correlations are found between temperature/relative humidity and the effective reproductive number (R value) in both China and the USA. CONCLUSIONS: Higher temperature and higher relative humidity potentially suppress the transmission of COVID-19. Specifically, an increase in temperature by 1°C is associated with a reduction in the R value of COVID-19 by 0.026 (95% CI (-0.0395 to -0.0125)) in China and by 0.020 (95% CI (-0.0311 to -0.0096)) in the USA; an increase in relative humidity by 1% is associated with a reduction in the R value by 0.0076 (95% CI (-0.0108 to -0.0045)) in China and by 0.0080 (95% CI (-0.0150 to -0.0010)) in the USA. Therefore, the potential impact of temperature/relative humidity on the effective reproductive number alone is not strong enough to stop the pandemic.