We evaluated two types of compounds for efficacy in inhibiting SARSCoV replication in vitro: calpain inhibitors (a class of cellular cysteine proteinases) and a number of nucleoside analogues. Cytopathic effect reduction assays visually determined with spectrophotometric verification by neutral red (NR) uptake assay were used to evaluate cytotoxicity and antiviral potency of the compounds. Significantly inhibitory compounds were then evaluated in virus yield reduction assays. Two calpain inhibitors, Val-Leu-CHO (calpain inhibitor VI) and Z-Val-Phe-Ala-CHO (calpain inhibitor III), were the most potent inhibitors of SARSCoV. By virus yield reduction assay, calpain inhibitor VI had a 90% effective concentration (EC90) of 3 μM and calpain inhibitor III had an EC90 of 15 μM. β-D-N4-hydroxycytidine was the most selective nucleoside analogue inhibitor with an EC90 of 6 μM by virus yield reduction assay. These compounds or analogues warrant further evaluation as potential therapies for treating SARS or could be used as lead compounds for discovery of more potent SARSCoV inhibitors.
The trend of declining voter turnout across the western world has led some in Canada to call for mandatory voting. Australia is often cited as a successful example of compulsory voting in a Westminster system. While the aim to increase voter turnout is noble, there are many non-coercive methods of improving democracy and voter turnout that Canada ought to adapt before resorting to mandatory voting. Assessed methods include electoral reform, lowering the voting age, and instituting online voting; all are non-coercive ways to improve public satisfaction with the political process in Canada. Additionally, mandatory voting reduces Canadians’ ability to abstain from participating in the political system should they choose to do so which could have important philosophical implications. Furthermore,voter turnout data for Australia does not take into account important differences between registered voter turnout and voting age population turnout. Importantly, when analyzed these numbers indicate that compulsory voting in Australia is not as successful as many believe. Despite its ostensible attraction as a clear way to increase voter turnout, a legal requirement to vote is not a panacea to the issues of political distrust, dissatisfaction, and disengagement in Canada that are the root causes of low voter turnout.
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