Antiviral Potential of Small Molecules Cordycepin, Thymoquinone, and N6, N6-Dimethyladenosine Targeting SARS-CoV-2 Entry Protein ADAM17.

COVID-19 is an acute respiratory disease caused by SARS-CoV-2 that has spawned a worldwide pandemic. ADAM17 is a sheddase associated with the modulation of the receptor ACE2 of SARS-CoV-2. Studies have revealed that malignant phenotypes of several cancer types are closely relevant to highly expressed ADAM17. However, ADAM17 regulation in SARS-CoV-2 invasion and its role on small molecules are unclear. Here, we evaluated the ADAM17 inhibitory effects of cordycepin (CD), thymoquinone (TQ), and N6, N6-dimethyladenosine (m62A), on cancer cells and predicted the anti-COVID-19 potential of the three compounds and their underlying signaling pathways by network pharmacology. It was found that CD, TQ, and m62A repressed the ADAM17 expression upon different cancer cells remarkably. Moreover, CD inhibited GFP-positive syncytia formation significantly, suggesting its potential against SARS-CoV-2. Pharmacological analysis by constructing CD-, TQ-, and m62A-based drug-target COVID-19 networks further indicated that ADAM17 is a potential target for anti-COVID-19 therapy with these compounds, and the mechanism might be relevant to viral infection and transmembrane receptors-mediated signal transduction. These findings imply that ADAM17 is of potentially medical significance for cancer patients infected with SARS-CoV-2, which provides potential new targets and insights for developing innovative drugs against COVID-19.

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2.

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals.

ISG20 inhibits viruses such as SARS-CoV-2 invasion; however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m6 2A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations; the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20-009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m6 2A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.

The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals

ISG20 inhibits viruses such as SARS-CoV-2 invasion;however, details of its expression and regulation with viral susceptibility remain to be elucidated. The present study analyzed ISG20 expression, isoform information, survival rate, methylation patterns, immune cell infiltration, and COVID-19 outcomes in healthy and cancerous individuals. Cordycepin (CD) and N6, N6-dimethyladenosine (m62A) were used to treat cancer cells for ISG20 expression. We revealed that ISG20 mRNA expression was primarily located in the bone marrow and lymphoid tissues. Interestingly, its expression was significantly increased in 11 different types of cancer, indicating that cancer patients may be less vulnerable to SARS-CoV-2 infection. Among them, higher expression of ISG20 was associated with a long OS in CESC and SKCM, suggesting that ISG20 may be a good marker for both viral prevention and cancer progress. ISG20 promoter methylation was significantly lower in BLCA, READ, and THCA tumor tissues than in the matched normal tissues, while higher in BRCA, LUSC, KIRC, and PAAD. Hypermethylation of ISG20 in KIRC and PAAD tumor tissues was correlated with higher expression of ISG20, suggesting that methylation of ISG20 may not underlie its overexpression. Furthermore, ISG20 expression was significantly correlated with immune infiltration levels, including immune lymphocytes, chemokine, receptors, immunoinhibitors, immunostimulators, and MHC molecules in pan-cancer. STAD exhibited the highest degree of ISG20 mutations;the median progression-free survival time in months for the unaltered group was 61.84, while it was 81.01 in the mutant group. Isoforms ISG20-001 and ISG20−009 showed the same RNase_T domain structure, demonstrating the functional roles in tumorigenesis and SARS-CoV-2 invasion inhibition in cancer patients. Moreover, CD and m62A increase ISG20 expression in various cancer cell lines, implying the antiviral/anti-SARS-CoV-2 therapeutic potential. Altogether, this study highlighted the value of combating cancer by targeting ISG20 during the COVID-19 pandemic, and small molecules extracted from traditional Chinese medicines, such as CD, may have potential as anti-SARS-CoV-2 and anticancer agents by promoting ISG20 expression.

Beyond bean counting: Is the policy effective for the innovation efficiency of wind power industry in China?

The technological innovation of wind power is crucial to energy security and energy structure transformation. The Chinese government has been committed to improving the innovation of the wind power industry for decades. Although academic researchers and wind power policymakers have been widely concerned about the absolute score of innovation output, concentrating on innovation output in isolation is ultimately insufficient. This article goes beyond bean counting and evaluates the innovation of the Chinese wind power industry from the perspective of relative efficiency, and then assesses the efforts of the government to improve innovation efficiency (IE). The study uses the data of 105 wind power listed enterprises in China over the period 2008–2019. According to the recommendation made by the existing papers, IE is defined as the capability to generate innovation outputs per unit of R&D investment. Regression analysis is applied to test the policy effect. During 2008–2019, the average value of IE of Chinese wind power industry is 0.196. The IE of wind power enterprises in eastern China (0.265) is higher than that in central and western China (0.169). Besides, the regression results indicate that all categories of wind power innovation policies contribute to the IE of wind power industry in China. Furthermore, the innovation policies issued by the departments of the State Council significantly improve the IE of wind power industry, but the innovation policies from the National People's Congress and the State Council have no significant impacts on IE. [ FROM AUTHOR] Copyright of Research Evaluation is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)