Cytokine release syndrome, a prominent mechanism of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19), can cause multiple bodily reactions, including excessive release of proinflammatory mediators, with tumor necrosis factor-α (TNF-α) being the most prevalent cytokine combined with persistently elevated D-dimer levels that are indicative of potential thrombotic events, low levels of endogenous nitric oxide (NO) generation, and progressive decrease in hemoglobin production. In our argument, the conceptual repurposing of hydroxyurea (HU) for managing COVID-19 can provide a promising therapeutic option originating from a rich history of investigational antiviral activity. HU as a proposed supportive therapeutic agent for treating COVID-19 can exemplify a successful remedial choice through its anti-inflammatory activity along with an intrinsic propensity to control the circulatory levels of key cytokines including TNF-α. HU has the ability to undergo in vivo NO conversion acting as NO donor together with being a prominent inducer of fetal hemoglobin (HbF) production. The combination of the mentioned two properties allows HU to possess evident capability of protecting against thrombotic events by controlling D-dimer levels. The implication of our hypothetical argument sheds light on the curative potential of HU, which can be strategically harnessed against COVID-19.
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