Wednesday, May 05, 2021 8:34:26 AM
The lectin-like human a defensin 5 (HD5) and HD6 peptides protect intestinal infections. Lectins are proteins or glycoproteins that specifically bind to carbohydrates present on the glycoproteins surface. 2019-nCoV S-proteins and its intestinal receptor ACE2 both are glycosylated proteins. HD5 binds to the ligand-binding domain (LBD) of ACE2 glycoproteins and masks its availability to enter the 2019-nCoV virus (Wang et al., 2019). This interruption between viral glycoproteins and cellular receptors activates the adaptive immune antigen-presenting phagocytes cells and interferes with nuclear enzymes that prevent viral cellular replication (Park et al., 2018). Human neutrophil peptide-4, bovine beta-defensin 1, HD5, HD6, rat neutrophil peptide 1 (RNP-1), RNP-2, chicken avian beta-defensin 5 (AvBD5), AvBD6, and channel catfish beta-defensin peptide have the antiviral activity against the Middle East Respiratory Syndrome Coronavirus [3]. HNP1-6, HD5-6, and HBD2-3 defensins remove the viruses by getting in the way of viral entry, membrane destabilisation, immune-modulating, downregulating receptors and ligands such as ACE2, CD4, CCR6 CXCR4, CXCL & CXCL5, lysosome fusion, inhibiting essential proteases, central dogma enzymes, and post assembly of virion particles (Park et al., 2018 [37]; Chang et al., 2005; [70].
Bio-computational designed Brilacidin is a synthetic non-peptide defensin mimic drug that destabilises the viral membrane by its amphipathic & hydrophobic nature, and its immunomodulatory property influence the expression of IL-1ß, IL-6, TNF-a cytokines, and cAMP& PDE4/PDE3 pathways which are associated with bronchodilator and anti-inflammatory effects of COVID-19 disease. The smaller size, more effective antimicrobial activity, bioavailability, low enzymatic degradation and toxicity, natural and low-cost production make the Brilacidin a most potent drug against SARS-CoV-2 than the known antiviral drugs. Dalbavancin, Telavancin, Oritavanci, and Roflumilast are other Brilacidin like drugs used for MERS, SARS, and SARS-CoV2 viral inhibitions [71]. Rhesus macaque's leukocytes express ?-defensin1 (RTD-1) and RTD-2 antimicrobial peptides in response to viral infections. HD5-6, HNP1-6, HBD2-6, and retrocyclin-2 inactivate the various enveloped and non-enveloped virion particles by interrupting virus pre and post-entry steps, chemokines, and cytokines immunomodulation, chemotaxis of immune cells [72].
https://www.sciencedirect.com/science/article/pii/S0882401021002023
Leo Ehrilich Quote "If Brilacidin goes on to realize its promise as a broad spectrum antiviral, the potential benefits to patients and shareholders for this drug would likely be greater than I or anyone could have ever imagined.”
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