Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework (preprint)

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Sustainable Development Goal 13 and Switching Priorities: Addressing Climate Change in the Context of Pandemic Recovery Efforts (preprint)

The COVID-19 pandemic has had many deep social and economic impacts that go beyond health issues. One consequence is that the pandemic has made it even harder to mobilize the financial resources needed to pursue SDG 13 (Climate Action) as a whole and to fund climate change mitigation and adaptation efforts in particular. This is especially acute in respect of the efforts to achieve the targets set by the Paris Agreement and by the recent decisions in Glasgow. This paper looks at how the COVID-19 pandemic has accelerated poverty and undermined climate change adaptation efforts, as a result of the switches in priorities and funding. Using a review of the recent literature, an analysis of international trends, and a survey among climate scientists, it identifies some of the impacts of the pandemic on climate change mitigation and adaptation efforts and discusses their implications. The findings indicate a decrease in funding to climate change research since the pandemic crisis. The bibliometric analysis reveals that a greater emphasis has been placed on the relationship between COVID-19 and poverty when compared to the interrelations between COVID-19 and climate change. Addressing climate change is as urgent now as it was since the pandemic crisis started, and efforts need to be made to upkeep the levels of funding needed to support research in this field.

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment (preprint)

Over 180.000 SARS-COV-2 positive cases have been confirmed in Italy as April 20, with the number of deaths exceeding 23 thousand, making Italy the second Country for world COVID-19 deaths. Such enormous occurrence of infected and dead people raises the urgent demand of effective fast available treatments to control and diminish this pandemic. Discovering the cellular/molecular mechanisms of SARS-COV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and for therapeutically approaching it. From literature data, through a bioinformatics approach, an in silico analysis was performed, to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. We thus investigate on the signaling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets and functions. We predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with deacetylate histones pathway HDAC. Our results matched with the available clinical data. We hypothesize the current and EMA-approved, SARS-COV-2 off-label, HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. A ranked list of compounds is given that can be tested.

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment (preprint)

Over 180.000 SARS-COV-2 positive cases have been confirmed in Italy as April 20, with the number of deaths exceeding 23 thousand, making Italy the second Country for world COVID-19 deaths. Such enormous occurrence of infected and dead people raises the urgent demand of effective fast available treatments to control and diminish this pandemic. Discovering the cellular/molecular mechanisms of SARS-COV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and for therapeutically approaching it. From literature data, through a bioinformatics approach, an in silico analysis was performed, to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. We thus investigate on the signaling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets and functions. We predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with deacetylate histones pathway HDAC. Our results matched with the available clinical data. We hypothesize the current and EMA-approved, SARS-COV-2 off-label, HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. A ranked list of compounds is given that can be tested.