SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.

The coronavirus disease 2019 (COVID-19) pandemic has devastated global health. Identifying key host factors essential for SARS-CoV-2 RNA replication is expected to unravel cellular targets for the development of broad-spectrum antiviral drugs which have been quested for the preparedness of future viral outbreaks. Here, we have identified host proteins that associate with nonstructural protein 12 (nsp12), the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 using a mass spectrometry (MS)-based proteomic approach. Among the candidate factors, CDK2 (Cyclin-dependent kinase 2), a member of cyclin-dependent kinases, interacts with nsp12 and causes its phosphorylation at T20, thus facilitating the assembly of the RdRp complex consisting of nsp12, nsp7 and nsp8 and promoting efficient synthesis of viral RNA. The crucial role of CDK2 in viral RdRp function is further supported by our observation that CDK2 inhibitors potently impair viral RNA synthesis and SARS-CoV-2 infection. Taken together, we have discovered CDK2 as a key host factor of SARS-CoV-2 RdRp complex, thus serving a promising target for the development of SARS-CoV-2 RdRp inhibitors.

Improved transfer efficiency of supercharged 36 + GFP protein mediate nucleic acid delivery.

The potential of nucleic acid therapeutics to treat diseases by targeting specific cells has resulted in its increasing number of uses in clinical settings. However, the major challenge is to deliver bio-macromolecules into target cells and/or subcellular locations of interest ahead in the development of delivery systems. Although, supercharged residues replaced protein 36 + GFP can facilitate itself and cargoes delivery, its efficiency is still limited. Therefore, we combined our recent progress to further improve 36 + GFP based delivery efficiency. We found that the penetration efficacy of 36 + GFP protein was significantly improved by fusion with CPP-Dot1l or treatment with penetration enhancer dimethyl sulfoxide (DMSO) in vitro. After safely packaged with plasmid DNA, we found that the efficacy of in vitro and in vivo transfection mediated by 36 + GFP-Dot1l fusion protein is also significantly improved than 36 + GFP itself. Our findings illustrated that fusion with CPP-Dot1l or incubation with DMSO is an alternative way to synergically promote 36 + GFP mediated plasmid DNA delivery in vitro and in vivo.

Optimizing the Practice Environment for Medical Staff in the Post-pandemic Era: A Discrete Choice Experiment.

Objective: This study aimed to elicit the stated job preferences of Chinese medical staff in the post-pandemic era and identify the relative importance of different factors in the practice environment. Methods: We used an online discrete choice experiment (DCE) survey instrument to elicit the job preferences of medical staff (doctors and nurses) in tertiary hospitals in Anhui, China. Attributes and levels were generated using qualitative methods, and four attributes were considered: career development, workload, respect from society, and monthly income. A set of profiles was created using a D-efficient design. The data were analyzed considering potential preference heterogeneity, using the conditional logit model and the latent class logit (LCL) model. Results: A total of 789 valid questionnaires were included in the analysis, with an effective response rate of 73.33%. Career development, workload, respect from society, and monthly income were significant factors that influenced job preferences. Three classes were identified based on the LCL model, and preference heterogeneity among different medical staff was demonstrated. Class 1 (16.17%) and Class 2 (43.51%) valued respect from society most, whereas Class 3 (40.32%) prioritized monthly income. We found that when respect from society was raised to a satisfactory level (50-75% positive reviews), the probability of medical staff choosing a certain job increased by 69.9%. Conclusion: Respect from society was the most preferred attribute, while workload, monthly income, and career development were all key factors in the medical staff's job choices. The heterogeneity of the medical professionals' preferences shows that effective policy interventions should be customized to accommodate these drive preferences.

Combating the COVID-19 pandemic: The role of disaster experience.

In this study, we provide evidence suggesting that in countries with severe disaster experience (SDE), the response to the coronavirus disease 2019 (COVID-19) pandemic is characterized by a higher level of attention in the population, more timely market responses, and stricter government containment measures. Specifically, we find that during the first COVID-19 outbreak in Wuhan, China, people in countries with SDE searched for related information more frequently on Google than did people in countries with mild disaster experience (MDE). Moreover, we find that a higher level of attention to COVID-19, as measured by Google search index usage, led to greater declines in stock market indexes in countries with SDE than in those with MDE. Finally, we find that compared with countries with MDE, those with SDE implemented more stringent social distancing policies in response to domestic COVID-19 outbreaks, and individuals in the latter group of countries were more likely to follow government-imposed rules of social distancing in both the early outbreak and reopening phases. Our findings suggest that disaster experience increases risk aversion and is an essential mechanism by which individuals, markets, and countries respond to COVID-19 in a timely manner.