Search

Drug repurposing is an important strategy in COVID-19 treatment, but many clinically approved compounds have not been extensively studied in the context of embryogenesis, thus limiting their administration during pregnancy. Here we used the zebrafish embryo model organism to test the effects of 162 marketed drugs on cardiovascular development. Among the compounds used in the clinic for COVD-19 treatment, we found that Remdesivir led to reduced body size and heart functionality at clinically relevant doses. Ritonavir and Baricitinib showed reduced heart functionality and Molnupiravir and Baricitinib showed effects on embryo activity. Sabizabulin was highly toxic at concentrations only 5 times higher than Cmax and led to a mean mortality of 20% at Cmax. Furthermore, we tested if zebrafish could be used as a model to study inflammatory response in response to spike protein treatment and found that Remdesivir, Ritonavir, Molnupiravir, Baricitinib as well as Sabizabulin counteracted the inflammatory response related gene expression upon SARS-CoV-2 spike protein treatment. Our results show that the zebrafish allows to study immune-modulating properties of COVID-19 compounds and highlights the need to rule out secondary defects of compound treatment on embryogenesis. All results are available on a user friendly web-interface https://share.streamlit.io/alernst/covasc%5fdataapp/main/CoVasc%5fDataApp.py that provides a comprehensive overview of all observed phenotypic effects and allows personalized search on specific compounds or group of compounds. Furthermore, the presented platform can be expanded for rapid detection of developmental side effects of new compounds for treatment of COVID-19 and further viral infectious diseases. [ABSTRACT FROM AUTHOR]

Swidden is often blamed for deforestation but research has shown that these traditional systems can have a role in maintaining and enhancing carbon stocks and therefore could be compatible with efforts such as payments for environmental services (PES) and Reducing Emissions from Deforestation and Forest Degradation (REDD+) schemes in Vietnam. This would require that PES and REDD+ project developers build on existing local governance structures. In this paper we attempt to understand such structures though analysis of information and resource exchange in two communities in Vietnam, focusing on traditional local governance guiding swidden practices, and mass organisations. Results show a high diversity of formal (government-formed networks) and informal (traditional) swidden governance structures that can be embedded in REDD+ and PES schemes, where geographical accessibility, socio-cultural practices, and capacities of government will also determine which structure will work best for swidden communities to participate in REDD+/PES. [ABSTRACT FROM AUTHOR]