evasins / University of Oxford, ILC Therap - LARVOL DELTA

Development of chemokine network inhibitors using combinatorial saturation mutagenesis. (PubMed, Commun Biol) - "Tick evasins overcome redundant pathways by broadly targeting either CC or CXC-chemokine classes...Using AlphaFold 3 to model peptide - chemokine interactions, we show that the combinatorially mutated peptide has increased total and hydrophobic inter-chain bonding via tryptophan residues and is predicted to sterically hinder chemokine interactions required for immune cell migration. We suggest that CoSMOS-generated promiscuous binding activities could target disease networks where structurally related proteins drive redundant signalling pathways."

Journal • Inflammation

Assessing customized multivalent chemokine-binding peptide treatment in a murine model of coxsackievirus B3 myocarditis. (PubMed, Basic Res Cardiol) - "Ticks have evolved chemokine-binding salivary proteins known as Evasins, which efficiently suppress inflammation...In survivors of acute CVB3 infection exhibiting manifestations of the subacute phase, BK1.3 enhances virus control, reduces myeloid cell infiltration in the heart and liver, improves markers of liver injury, and alleviates cardiac dysfunction, as evidenced by echocardiographic global longitudinal strain analysis. These findings affirm the safety profile of BK1.3 peptide therapeutics in a preclinical mouse model of acute CVB3 infection and emphasize its potential for therapeutic advancement in addressing virus-induced inflammation in the heart."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hepatology • Hypoglycemia • Infectious Disease • Inflammation • Liver Failure • Pancreatitis • CCL2 • CCL3 • CCL8

Discovery and pharmacophoric characterization of chemokine network inhibitors using phage-display, saturation mutagenesis and computational modelling. (PubMed, Nat Commun) - "AlphaFold2-Multimer modelling suggests that the peptide occludes distinct receptor-binding regions in CC and in CXC-chemokines, with the first and second motifs contributing ionic and hydrophobic interactions respectively. Our results indicate that peptides with broad-spectrum anti-chemokine activity and therapeutic potential may be identified from evasins, and the pharmacophore characterised by phage display, saturation mutagenesis and computational modelling."

Journal • Inflammation

Editorial: Tick Saliva: Secret to Blood Feeding Success. (PubMed, Front Cell Infect Microbiol) - No abstract available

Journal

Phylogenetic Analysis Indicates That Evasin-Like Proteins of Ixodid Ticks Fall Into Three Distinct Classes. (PubMed, Front Cell Infect Microbiol) - "Most evasins/evasin-like proteins in Metastriate ticks belong to class A1, whereas in Prostriate species they are predominantly class B. In keeping with this, the majority of biochemically characterized Metastriate evasins bind CC-chemokines, whereas the majority of Prostriate evasins bind CXC-chemokines. While the origin of the structurally dissimilar classes A1 and A2 is yet unresolved, these results suggest that class B evasin-like proteins arose before the divergence of Prostriate and Metastriate lineages and likely functioned to neutralize CXC-chemokines and support blood feeding."

Journal • Immunology • Infectious Disease • Inflammation

Monoclonal antibodies targeting nonstructural viral antigens can activate ADCC against human cytomegalovirus. (PubMed, J Clin Invest) - "We now show that the addition of anti-HCMV antibodies (Abs) can activate NK cells prior to the production of new virions, through Ab-dependent cellular cytotoxicity (ADCC), overcoming viral immune evasins...Cloned Abs targeting a single antigen (UL141) were sufficient to mediate ADCC against HCMV-infected cells, even at low concentrations. Collectively, these findings validated an unbiased methodological approach to the identification of immunodominant viral antigens, providing a pathway toward an immunotherapeutic strategy against HCMV and potentially other pathogens."

Journal • Cytomegalovirus Infection • Immunology

TickSialoFam (TSFam): A Database That Helps to Classify Tick Salivary Proteins, a Review on Tick Salivary Protein Function and Evolution, With Considerations on the Tick Sialome Switching Phenomenon. (PubMed, Front Cell Infect Microbiol) - "Not only do these gene products belong to many expanded families, such as the lipocalins, metalloproteases, Antigen-5, cystatins, and apyrases, but also families that are found exclusively in ticks, such as the evasins, Isac, DAP36, and many others...The TSA database identified 136 tick salivary secreted protein families, as well as 80 families of endosomal-related products, mostly having a protein modification function. As the number of sequences increases, and new annotation details become available, new releases of the TSF database may become available."

Journal • DAXX

Semisynthesis of an evasin from tick saliva reveals a critical role of tyrosine sulfation for chemokine binding and inhibition. (PubMed, Proc Natl Acad Sci U S A) - "Comparisons of evasin sequences and structural data suggest that tyrosine sulfation serves as a receptor mimetic strategy for recognizing and suppressing the proinflammatory activity of a wide variety of mammalian chemokines. As such, the incorporation of this posttranslational modification (PTM) or mimics thereof into evasins may provide a strategy to optimize tick salivary proteins for antiinflammatory applications."

Journal

Structural characterization of anti-CCL5 activity of the tick salivary protein Evasin-4. (PubMed, J Biol Chem) - "The crucial part of this strategy is expression of a broad family of salivary proteins, called Evasins, to neutralize chemokines responsible for cell trafficking and recruitment...The peptide derived from the N-terminal region of Evasin-4 possessed nM affinity to CCL5 and inhibited CCL5 activity in monocyte migration assays. This suggests that Evasin-4 derivatives could be used as starting point for the development of anti-inflammatory drugs."

Journal • Atherosclerosis • CCL5

Engineered anti-inflammatory peptides inspired by mapping an evasin-chemokine interaction. (PubMed, J Biol Chem) - "We show that local as well as systemic administration of BK1.3 potently blocks inflammation in vivo. Identification and characterization of the chemokine-binding interface of evasins could thus inspire the development of novel anti-inflammatory peptides that therapeutically target the chemokine network in inflammatory diseases."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Immunology • CCL2 • CCL3 • CCL7