Evaluation of the early-stage entrepreneurship activity in the United States during the COVID-19 pandemic

This paper examines the effects of the COVID-19 pandemic (measured by total cases and deaths per 100K people) on the early-stage entrepreneurship activity (measured by the Kauffman Early-Stage Entrepreneurship indicators) in the United States. The empirical analyses are based on the panel dataset of 51 States between 2020 and 2021. The findings show that the COVID-19 pandemic negatively affects early-stage entrepreneurship activity. Further analyses indicate the positive impact of the COVID-19 pandemic on the startup's early survival rate. However, new entrepreneurs' rate and opportunity share are negatively affected by the COVID-19 pandemic. Implications for the post-COVID-19 era are also discussed.

Stochastic Dynamics of the COVID-19 Case-Fatality Ratios in Indonesia, Malaysia, and the Philippines: Economic Implications for the Post-COVID-19 Era.

This paper analyses the stochastic dynamics of the COVID-19 Case-Fatality Ratios (CFR) in three developing economies in East Asia: Indonesia, Malaysia, and the Philippines. The sample covers the daily frequency data from April 28, 2020, to June 29, 2021. For this purpose, we utilize two unit root tests, which consider one structural break and two structural breaks. The findings reveal that the CFR follows a unit root process in Indonesia and the Philippines. However, the CFR is stationary in Malaysia. This evidence indicates that the COVID-19 has a permanent effect in Indonesia and the Philippines but temporary in Malaysia. The paper also discusses the potential economic implications of these results for the post-COVID-19 era in the related developing economies.

Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.

Exploring The Molecular Mechanisms of Classical Hodgkin Lymphoma Through Bioinformatics Analysis (preprint)

Background Classic Hodgkin lymphoma (CHL) is the most common HL in the modern society. Although the treatment of cHL has made great progress, its molecular mechanisms have yet to be deciphered.Objectives The purpose of this study is to find out the crucial potential genes and pathways associated with cHL.Methods We downloaded the cHL microarray dataset (GSE12453) from Gene Expression Omnibus (GEO) database and to identify the differentially expressed genes (DEGs) between cHL samples and normal samples through the limma package in R. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs were carried out. Finally, we constructed the protein-protein interaction network to screen out the hub genes using Search Tool for the Retrieval of Interacting Genes (STRING) database.Results We screened out 788 DEGs in the cHL dataset, such as BATF3, IER3, RAB13 and FCRL2. GO functional enrichment analysis indicated that the DEGs were related with regulation of lymphocyte activation, secretory granule lumen and chemokine activity. KEGG pathway analysis showed that the genes enriched in Prion disease, Complement and coagulation cascades and Parkinson disease Coronavirus disease-COVID-19 pathway. Protein-protein interaction network construction identified 10 hub genes (IL6, ITGAM, CD86, FN1, MMP9, CXCL10, CCL5, CD19, IFNG, SELL, UBB) in the network.Conclusions In the present investigation, we identified several pathways and hub genes related to the occurrence and development of cHL, which may provide an important basis for further research and novel therapeutic targets and prognostic indicators for cHL.

A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2.

A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3Cpro) of enterovirus 71 (EV71). Most of the compounds exhibited high antiviral activity, and among them, compound 18p demonstrated potent enzyme inhibitory activity and broad-spectrum antiviral activity on a panel of enteroviruses and rhinoviruses. The crystal structure of EV71 3Cpro in complex with 18p determined at a resolution of 1.2 Å revealed that 18p covalently linked to the catalytic Cys147 with an aldehyde group. In addition, these compounds also exhibited good inhibitory activity against the 3CLpro and the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially compound 18p (IC50 = 0.034 µM, EC50 = 0.29 µM). According to our previous work, these compounds have no reasons for concern regarding acute toxicity. Compared with AG7088, compound 18p also exhibited good pharmacokinetic properties and more potent anticoronavirus activity, making it an excellent lead for further development.

Causal Relationship Between the Spread of the COVID-19 and Geopolitical Risks in Emerging Economies.

This study investigates the causality between the spread of the COVID-19 pandemic (measured by new cases per million and new deaths per million) and geopolitical risks (measured by the index of geopolitical risks). We use the balanced panel data framework in 18 emerging economies from January 2020 to August 2020. We run the initial tests of cross-sectional dependence and the panel unit root tests with capturing cross-sectional dependence. Then, we utilize the panel Granger non-causality tests for heterogeneous stationary panel datasets. According to the findings, there is a significant causality from both measures of spreading the COVID-19 pandemic to geopolitical risks. Further tests are performed, and potential implications are also discussed.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2.

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC50 of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.