Public Health Needs the Public Trust: A Pandemic Retrospective

The COVID crisis of the past three years has greatly impacted stakeholder relationships between scientists, health providers, policy makers, pharmaceutical industry employees, and the public. Lockdowns and restrictions of civil liberties strained an already fraught relationship between the public and policy makers, with scientists also seen as complicit in providing the justification for the abrogation of civil liberties. This was compounded by the suppression of open debate over contentious topics of public interest and a violation of core bioethical principles embodied in the Nuremberg Code. Overall, the policies chosen during the pandemic have had a corrosive impact on public trust, which is observable in surveys and consumer behaviour. While a loss of trust is difficult to remedy, the antidotes are accountability and transparency. This narrative review presents an overview of key issues that have motivated public distrust during the pandemic and ends with suggested remedies. Scientific norms and accountability must be restored in order to rebuild the vital relationship between scientists and the public they serve

DataSheet1_Therapeutic potential of compounds targeting SARS-CoV-2 helicase.docx

The economical and societal impact of COVID-19 has made the development of vaccines and drugs to combat SARS-CoV-2 infection a priority. While the SARS-CoV-2 spike protein has been widely explored as a drug target, the SARS-CoV-2 helicase (nsp13) does not have any approved medication. The helicase shares 99.8% similarity with its SARS-CoV-1 homolog and was shown to be essential for viral replication. This review summarizes and builds on existing research on inhibitors of SARS-CoV-1 and SARS-CoV-2 helicases. Our analysis on the toxicity and specificity of these compounds, set the road going forward for the repurposing of existing drugs and the development of new SARS-CoV-2 helicase inhibitors.</p

Identifying Inhibitors of &minus;1 Programmed Ribosomal Frameshifting in a Broad Spectrum of Coronaviruses

Recurrent outbreaks of novel zoonotic coronavirus (CoV) diseases in recent years have highlighted the importance of developing therapeutics with broad-spectrum activity against CoVs. Because all CoVs use &minus;1 programmed ribosomal frameshifting (&minus;1 PRF) to control expression of key viral proteins, the frameshift signal in viral mRNA that stimulates &minus;1 PRF provides a promising potential target for such therapeutics. To test the viability of this strategy, we explored whether small-molecule inhibitors of &minus;1 PRF in SARS-CoV-2 also inhibited &minus;1 PRF in a range of bat CoVs&mdash;the most likely source of future zoonoses. Six inhibitors identified in new and previous screens against SARS-CoV-2 were evaluated against the frameshift signals from a panel of representative bat CoVs as well as MERS-CoV. Some drugs had strong activity against subsets of these CoV-derived frameshift signals, while having limited to no effect on &minus;1 PRF caused by frameshift signals from other viruses used as negative controls. Notably, the serine protease inhibitor nafamostat suppressed &minus;1 PRF significantly for multiple CoV-derived frameshift signals. These results suggest it is possible to find small-molecule ligands that inhibit &minus;1 PRF specifically in a broad spectrum of CoVs, establishing frameshift signals as a viable target for developing pan-coronaviral therapeutics