Journal
BIOMEDICINES
Volume 9, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/biomedicines9121867
Keywords
SARS-CoV2; COVID-19; PAD; NET
Categories
Funding
- Mark Linder Walk for the Mind, Illinois Neurological Institute, OSF foundation, Peoria, IL
- KB Strong Foundation, Washington, IL
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The evolution of variants of SARS-CoV-2 presents challenges to vaccine efficacy, necessitating the development of pharmacotherapeutics specific to the pathophysiology of the virus. Peptidylarginine deiminases (PADs) and their inhibitors may play a crucial role in reducing thrombotic complications in COVID-19 patients.
Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus's dynamicity has resulted in the evolution of various variants, including the delta variant and the more novel mu variant. With a multitude of mutant strains posing as challenges to vaccine efficacy, it is critical that researchers embrace the development of pharmacotherapeutics specific to SARS-CoV-2 pathophysiology. Neutrophil extracellular traps and their constituents, including citrullinated histones, display a linear connection with thrombotic manifestations in COVID-19 patients. Peptidylarginine deiminases (PADs) are a group of enzymes involved in the modification of histone arginine residues by citrullination, allowing for the formation of NETs. PAD inhibitors, specifically PAD-4 inhibitors, offer extensive pharmacotherapeutic potential across a broad range of inflammatory diseases such as COVID-19, through mediating NETs formation. Although numerous PAD-4 inhibitors exist, current literature has not explored the depth of utilizing these inhibitors clinically to treat thrombotic complications in COVID-19 patients. This review article offers the clinical significance of PAD-4 inhibitors in reducing thrombotic complications across various inflammatory disorders like COVID-19 and suggests that these inhibitors may be valuable in treating the origin of SARS-CoV-2 immunothrombosis.
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