ABSTRACT
The decrease in the economic activity level around the world due to the COVID-19 pandemic spread has led to a sharp decrease in the crude oil price and provoked an oil war outbreak in the global energy market. The current situation has provoked the need for a total decrease in the crude oil production in the world. Considering that Russia is one of the main oil exporters on the world market, the need to determine the supply and demand levels for Russian oil is becoming relevant. The aim of the paper is to model predictive scenarios of Russian oil industry development, considering the specifics of the current economic environment given the COVID-19 pandemic. The multifactor correlation modeling method was used to form the system of indicators determining the level of demand and supply for Russian oil used and the total level of their influence. The functions determine the probability of implementing various scenarios of oil industry development depending on the predicted values of demand and supply. The three-sigma rule and the fuzzy sets method were used to estimate three scenarios of oil industry development for 2020–2021. Changes in revenues of the industry under the influence of forecast indicators of supply and demand for oil have been assessed and the probability of implementation of each of the scenarios has been reasoned. The results obtained are of a practical nature and can be used by government agencies, financial intermediaries, and scientists to diagnose Russian oil industry development. The results will be useful for oil companies to develop a strategy of open innovations for further design of the scientific information field for the effective functioning of the industry in complete uncertainty conditions.
ABSTRACT
Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo , Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro , SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.
ABSTRACT
Drug repurposing has the advantage of identifying potential treatments on a shortened timescale. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high-content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. Elevated MUC1 levels predict the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. Our screen identifies fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, fostamatinib reduces MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by the active metabolite R406 promotes MUC1 removal from the cell surface. Our work suggests fostamatinib as a repurposing drug candidate for ALI.
ABSTRACT
The decrease in the economic activity level around the world due to the COVID-19 pandemic spread has led to a sharp decrease in the crude oil price and provoked an oil war outbreak in the global energy market. The current situation has provoked the need for a total decrease in the crude oil production in the world. Considering that Russia is one of the main oil exporters on the world market, the need to determine the supply and demand levels for Russian oil is becoming relevant. The aim of the paper is to model predictive scenarios of Russian oil industry development, considering the specifics of the current economic environment given the COVID-19 pandemic. The multifactor correlation modeling method was used to form the system of indicators determining the level of demand and supply for Russian oil used and the total level of their influence. The functions determine the probability of implementing various scenarios of oil industry development depending on the predicted values of demand and supply. The three-sigma rule and the fuzzy sets method were used to estimate three scenarios of oil industry development for 2020-2021. Changes in revenues of the industry under the influence of forecast indicators of supply and demand for oil have been assessed and the probability of implementation of each of the scenarios has been reasoned. The results obtained are of a practical nature and can be used by government agencies, financial intermediaries, and scientists to diagnose Russian oil industry development. The results will be useful for oil companies to develop a strategy of open innovations for further design of the scientific information field for the effective functioning of the industry in complete uncertainty conditions.
ABSTRACT
Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo , Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro , SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.