Intervention of viral infections by targeting host cellular protease A proposition based on viral glycoprotein processing
Bibliographic record
Abstract
Interdisciplinary School of Health Sciences, Department of Health Science, Chronic Disease Program, Ottawa Hospital Research Institute, U Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada Department of Chemical Engineering, McGill University, Montreal, Canada <em>E-mail</em> : abasa2@uottawa.ca <em>Manuscript received 24 July 2013, accepted 25 July 2013</em> During the past century our world has witnessed a number of global pandemic outbreaks of viral infections from time to time, often with deadly consequences. However, in recent years viral infections of new types or variants are beginning to emerge often with significantly high virulence properties. A number of these new strains are derived from animals such as avian, cattle, primates, etc. which have crossed the animal barrier due to varying reasons that may include the change in lifestyle, food habit, increased migration, globalization as well as living and staying too close to animals. Extensive research has been undertaken to better understand the genetic and protein architectures of these and other highly infectious viruses and their mode of progression. Already potential targets have been identified for development of safe and effective intervention and treatment strategies. <em>\(These\) \(are\) \(all\) \(directed\) \(towards\) \(the\) \(viral \) \(components\) \(such\) \(as\)</em> <em>\(viral\) \(enzyme,\) \(viral\) \(protein\) \(and\) \(viral\) \(membrane\) \(associated\) \(with\) \(the\) \(fusiogenic\) </em>\(event.\) However, host cellular enzyme/s of protease family also plays a critical role in viral pathogenesis and infection. It cleaves viral surface glycoproteins leading to their maturation forms to be recognized by host cellular receptor. This leads to viral fusion with host membrane and delivery of its components leading to viral replication and progression. As a result, these selected host proteases may also be considered as important targets for blockade of viral infection and pathogenesis. In this respect, one enzyme in particular called furin (also known as PCSK3) that belongs to the Proprotein Convertase Subtilisin Kexin (PCSK) super family stands out the most. In fact, furin inhibitors have been developed and shown<em> in vitro</em> and animal models to diminish viral replication and its load. Development of highly selective furin inhibitors is thus an attractive .option to fight against the viral infections despite the challenge one has to face in terms of enzyme specificity, potency and delivery of anti-furin agents in an organ/tissue-specific manner. This review discusses the various issues facing this approach. Both pros and cons of this methodology are discussed and debated in this review.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".