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Table 2. Characterization of human neutrophil elastase inhibitors approved for use and in clinical trials
Name Therapeutic application Development phase Features
Prolastin® α1-antitrypsin deficiency and clinical evidence of FDA approved peptide reversible NE inhibitor
[15]
(α1-antitrypsin) emphysema recommended dose: 60 mg/kg body
weight once a week (for Prolastin-C
Liquid)
Elaspol® acute lung injury and acute respiratory distress approved for use in Japan non-peptide competitive NE inhibitor
(Sivelestat/ syndrome associated with the systemic inflammatory and South Korea IC 44 nM; K 200 nM
50
i
ONO-5046) [35] response syndrome
Alvelestat bronchiolitis obliterans syndrome II phase clinical trials reversible oral NE inhibitor
[15]
(AZD9668) IC 12 nM; K 9.4 nM
50 i
BAY 85-8501 [15] non-cystic fibrosis bronchiectasis II phase clinical trials reversible NE inhibitor, IC 0.065 nM;
50
K 0.08 nM
i
NE: Neutrophil elastase.

Figure 17. Synthetic substrates of CatG.

regarding NSP4 biology, substrate specificity and inhibitors development have been done. However, still,
blank spots remain to be filled. NSP4, unlike other NSPs, has been conserved for over 400 million years
from bony fish to humans . NSP4 is the only known enzyme that cleaves substrates with post-
[86]
translationally modified arginine residues, such as methylarginine and citrulline . These attributes suggest
[87]
that NSP4 could have another potential function, not typical of NSPs. In 2020, AhYoung et al. demonstrated
that NSP4 plays an essential role in mast cell biology . Their studies have shown/showed that NSP4 is
[88]
present during early mast cell development and is critical for the regulation of levels of histamine and
serotonin in the secretory granules of the developing mast cells. They discovered that NSP4 deficiency
causes protection against mast cell/histamine-dependent vascular leakage. These findings open new