The last three decades of research into tick salivary components have revealed several proteins with important pharmacological and immunological activities. Two primary interests have driven research into tick salivary secretions: the search for suitable pathogen transmission blocking or "anti-tick" vaccine candidates and the search for novel therapeutics derived from tick salivary components. Intensive basic research in the field of tick salivary gland transcriptomics and proteomics has identified several major protein families that play important roles in tick feeding and overcoming vertebrate anti-tick responses. Moreover, these families contain members with unrealized therapeutic potential. Here we review the major tick salivary protein families exploitable in medical applications such as immunomodulation, inhibition of hemostasis and inflammation. Moreover, we discuss the potential, opportunities, and challenges in searching for novel tick-derived drugs.

Department of Medical Biology Faculty of Science University of South Bohemia in České Budějovice České Budějovice Czechia

Laboratory of Genomics and Proteomics of Disease Vectors Biology Centre CAS Institute of Parasitology České Budějovice Czechia

Zobrazit více v PubMed

Anguita J., Ramamoorthi N., Hovius J. W., Das S., Thomas V., Persinski R., et al. (2002). Salp15, an ixodes scapularis salivary protein, inhibits CD4(+) T cell activation. PubMed DOI

Assumpcao T. C., Mizurini D. M., Ma D., Monteiro R. Q., Ahlstedt S., Reyes M., et al. (2018). Ixonnexin from tick saliva promotes fibrinolysis by interacting with plasminogen and tissue-type plasminogen activator, and prevents arterial thrombosis. PubMed DOI PMC

Assumpcao T. C., Ribeiro J. M., Francischetti I. M. (2012). Disintegrins from hematophagous sources. PubMed DOI PMC

Bania J., Stachowiak D., Polanowski A. (1999). Primary structure and properties of the cathepsin G/chymotrypsin inhibitor from the larval hemolymph of PubMed DOI

Barboza T., Gomes T., Mizurini D. M., Monteiro R. Q., Konig S., Francischetti I. M., et al. (2015). (99m)Tc-ixolaris targets glioblastoma-associated tissue factor: in vitro and pre-clinical applications. PubMed DOI

Beaufays J., Adam B., Menten-Dedoyart C., Fievez L., Grosjean A., Decrem Y., et al. (2008). Ir-LBP, an ixodes ricinus tick salivary LTB4-binding lipocalin, interferes with host neutrophil function. PubMed DOI PMC

Berggoetz M., Schmid M., Ston D., Wyss V., Chevillon C., Pretorius A. M., et al. (2014). Protozoan and bacterial pathogens in tick salivary glands in wild and domestic animal environments in South Africa. PubMed DOI

Blisnick A. A., Foulon T., Bonnet S. I. (2017). Serine protease inhibitors in ticks: an overview of their role in tick biology and tick-borne pathogen transmission. PubMed DOI PMC

Bonvin P., Power C. A., Proudfoot A. E. (2016). Evasins: therapeutic potential of a new family of chemokine-binding proteins from ticks. PubMed DOI PMC

Braunersreuther V., Montecucco F., Pelli G., Galan K., Proudfoot A. E., Belin A., et al. (2013). Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice. PubMed DOI

Brocklebank V., Kavanagh D. (2017). Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea. PubMed DOI PMC

Carneiro-Lobo T. C., Konig S., Machado D. E., Nasciutti L. E., Forni M. F., Francischetti I. M., et al. (2009). Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model. PubMed DOI PMC

Castor M. G., Rezende B., Resende C. B., Alessandri A. L., Fagundes C. T., Sousa L. P., et al. (2010). The CCL3/macrophage inflammatory protein-1alpha-binding protein evasin-1 protects from graft-versus-host disease but does not modify graft-versus-leukemia in mice. PubMed DOI

Charo I. F., Ransohoff R. M. (2006). The many roles of chemokines and chemokine receptors in inflammation. PubMed DOI

Chen Z., Wang B., Hu J., Yang W., Cao Z., Zhuo R., et al. (2013). SjAPI, the first functionally characterized Ascaris-type protease inhibitor from animal venoms. PubMed DOI PMC

Cherniack E. P. (2011). Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders. PubMed

Chmelar J., Calvo E., Pedra J. H., Francischetti I. M., Kotsyfakis M. (2012). Tick salivary secretion as a source of antihemostatics. PubMed DOI PMC

Chmelar J., Kotal J., Kopecky J., Pedra J. H. F., Kotsyfakis M. (2016). All for one and one for all on the tick-host battlefield. PubMed DOI PMC

Chmelar J., Kotal J., Langhansova H., Kotsyfakis M. (2017). Protease inhibitors in tick saliva: the role of serpins and cystatins in tick-host-pathogen interaction. PubMed DOI PMC

Chudzinski-Tavassi A. M., De-Sa-Junior P. L., Simons S. M., Maria D. A., De Souza Ventura J., Batista I. F., et al. (2010). A new tick Kunitz type inhibitor, Amblyomin-X, induces tumor cell death by modulating genes related to the cell cycle and targeting the ubiquitin-proteasome system. PubMed DOI

Chudzinski-Tavassi A. M., Maria D. A., Batista I. F., Ho P. L. (2005).

Cierpicki T., Bania J., Otlewski J. (2000). NMR solution structure of Apis mellifera chymotrypsin/cathepsin G inhibitor-1 (AMCI-1): structural similarity with PubMed DOI PMC

Coipan E. C., Jahfari S., Fonville M., Maassen C. B., Van Der Giessen J., Takken W., et al. (2013). Spatiotemporal dynamics of emerging pathogens in questing PubMed DOI PMC

Copin J. C., Da Silva R. F., Fraga-Silva R. A., Capettini L., Quintao S., Lenglet S., et al. (2013). Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice. PubMed DOI PMC

Corral-Rodriguez M. A., Macedo-Ribeiro S., Barbosa Pereira P. J., Fuentes-Prior P. (2009). Tick-derived Kunitz-type inhibitors as antihemostatic factors. PubMed DOI

Couillin I., Maillet I., Vargaftig B. B., Jacobs M., Paesen G. C., Nuttall P. A., et al. (2004). Arthropod-derived histamine-binding protein prevents murine allergic asthma. PubMed DOI

Dai J., Wang P., Adusumilli S., Booth C. J., Narasimhan S., Anguita J., et al. (2009). Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent. PubMed DOI PMC

Das S., Banerjee G., Deponte K., Marcantonio N., Kantor F. S., Fikrig E. (2001). Salp25D, an PubMed DOI

de Castro M. H., De Klerk D., Pienaar R., Latif A. A., Rees D. J., Mans B. J. (2016). De novo assembly and annotation of the salivary gland transcriptome of PubMed DOI

De Groot A. S., Scott D. W. (2007). Immunogenicity of protein therapeutics. PubMed DOI

de Souza J. G., Morais K. L., Angles-Cano E., Boufleur P., De Mello E. S., Maria D. A., et al. (2016). Promising pharmacological profile of a Kunitz-type inhibitor in murine renal cell carcinoma model. PubMed DOI PMC

Decrem Y., Rath G., Blasioli V., Cauchie P., Robert S., Beaufays J., et al. (2009). Ir-CPI, a coagulation contact phase inhibitor from the tick PubMed DOI PMC

Dehhaghi M., Kazemi Shariat Panahi H., Holmes E. C., Hudson B. J., Schloeffel R., Guillemin G. J. (2019). Human tick-borne diseases in Australia. PubMed DOI PMC

den Dunnen J., Gringhuis S. I., Geijtenbeek T. B. (2009). Innate signaling by the C-type lectin DC-SIGN dictates immune responses. PubMed DOI PMC

Deruaz M., Bonvin P., Severin I. C., Johnson Z., Krohn S., Power C. A., et al. (2013). Evasin-4, a tick-derived chemokine-binding protein with broad selectivity can be modified for use in preclinical disease models. PubMed DOI PMC

Deruaz M., Frauenschuh A., Alessandri A. L., Dias J. M., Coelho F. M., Russo R. C., et al. (2008). Ticks produce highly selective chemokine binding proteins with antiinflammatory activity. PubMed DOI PMC

El-Tantawy N. L. (2015). Helminthes and insects: maladies or therapies. PubMed DOI

Esteves E., Maruyama S. R., Kawahara R., Fujita A., Martins L. A., Righi A. A., et al. (2017). Analysis of the salivary gland transcriptome of unfed and partially fed amblyomma sculptum ticks and descriptive proteome of the saliva. PubMed DOI PMC

Francischetti I. M., Mather T. N., Ribeiro J. M. (2003). Cloning of a salivary gland metalloprotease and characterization of gelatinase and fibrin(ogen)lytic activities in the saliva of the Lyme disease tick vector PubMed DOI PMC

Francischetti I. M., Meng Z., Mans B. J., Gudderra N., Hall M., Veenstra T. D., et al. (2008). An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, PubMed DOI PMC

Francischetti I. M., My Pham V., Mans B. J., Andersen J. F., Mather T. N., Lane R. S., et al. (2005). The transcriptome of the salivary glands of the female western black-legged tick PubMed DOI PMC

Francischetti I. M., Sa-Nunes A., Mans B. J., Santos I. M., Ribeiro J. M. (2009). The role of saliva in tick feeding. PubMed DOI PMC

Frauenschuh A., Power C. A., Deruaz M., Ferreira B. R., Silva J. S., Teixeira M. M., et al. (2007). Molecular cloning and characterization of a highly selective chemokine-binding protein from the tick PubMed DOI

Fredslund F., Laursen N. S., Roversi P., Jenner L., Oliveira C. L., Pedersen J. S., et al. (2008). Structure of and influence of a tick complement inhibitor on human complement component 5. PubMed DOI

Garg R., Juncadella I. J., Ramamoorthi N., Ashish Ananthanarayanan S. K., Thomas V., Rincón M., et al. (2006). Cutting edge: CD4 is the receptor for the tick saliva immunosuppressor, Salp15. PubMed DOI PMC

Goodship T. H. J., Pinto F., Weston-Davies W. H., Silva J., Nishimura J. I., Nunn M. A., et al. (2017). Use of the complement inhibitor coversin to treat HSCT-associated TMA. PubMed DOI PMC

Grammer A. C., Lipsky P. E. (2017). Drug repositioning strategies for the identification of novel therapies for rheumatic autoimmune inflammatory diseases. PubMed DOI

Guo X., Booth C. J., Paley M. A., Wang X., Deponte K., Fikrig E., et al. (2009). Inhibition of neutrophil function by two tick salivary proteins. PubMed DOI PMC

Hammer J. F., Jenkins C., Bogema D., Emery D. (2016). Mechanical transfer of Theileria orientalis: possible roles of biting arthropods, colostrum and husbandry practices in disease transmission. PubMed DOI PMC

Hayward J., Sanchez J., Perry A., Huang C., Rodriguez Valle M., Canals M., et al. (2017). Ticks from diverse genera encode chemokine-inhibitory evasin proteins. PubMed DOI PMC

Hovius J. W., De Jong M. A., Den Dunnen J., Litjens M., Fikrig E., Van Der Poll T., et al. (2008). Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PubMed DOI PMC

Huang C., Zheng C., Li Y., Wang Y., Lu A., Yang L. (2014). Systems pharmacology in drug discovery and therapeutic insight for herbal medicines. PubMed DOI

Huang K., Strynadka N. C., Bernard V. D., Peanasky R. J., James M. N. (1994). The molecular structure of the complex of PubMed DOI

Izaguirre G., Arciniega M., Quezada A. G. (2019). Specific and selective inhibitors of proprotein convertases engineered by transferring serpin b8 reactive-site and exosite determinants of reactivity to the serpin alpha1PDX. PubMed DOI PMC

Izaguirre G., Qi L., Lima M., Olson S. T. (2013). Identification of serpin determinants of specificity and selectivity for furin inhibition through studies of alpha1PDX (alpha1-protease inhibitor Portland)-serpin B8 and furin active-site loop chimeras. PubMed DOI PMC

Jahfari S., Hofhuis A., Fonville M., Van Der Giessen J., Van Pelt W., Sprong H. (2016). Molecular detection of tick-borne pathogens in humans with tick bites and erythema migrans, in the Netherlands. PubMed DOI PMC

Jokerst J. V., Lobovkina T., Zare R. N., Gambhir S. S. (2011). Nanoparticle PEGylation for imaging and therapy. PubMed DOI PMC

Jongejan F., Uilenberg G. (2004). The global importance of ticks. PubMed

Jorgensen J. T. (2011). A challenging drug development process in the era of personalized medicine. PubMed DOI

Juncadella I. J., Anguita J. (2009). The immunosuppresive tick salivary protein, Salp15. PubMed DOI

Juncadella I. J., Bates T. C., Suleiman R., Monteagudo-Mera A., Olson CM.,, Jr., Navasa N., et al. (2010). The tick saliva immunosuppressor, Salp15, contributes to Th17-induced pathology during experimental autoimmune encephalomyelitis. PubMed DOI PMC

Juncadella I. J., Garg R., Ananthnarayanan S. K., Yengo C. M., Anguita J. (2007). T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. PubMed DOI

Juncadella I. J., Garg R., Bates T. C., Olivera E. R., Anguita J. (2008). The Ixodes scapularis salivary protein, salp15, prevents the association of HIV-1 gp120 and CD4. PubMed DOI PMC

Karczewski J., Connolly T. M. (1997). The interaction of disagregin with the platelet fibrinogen receptor, glycoprotein IIb-IIIa. PubMed DOI

Karczewski J., Endris R., Connolly T. M. (1994). Disagregin is a fibrinogen receptor antagonist lacking the Arg-Gly-Asp sequence from the tick, PubMed

Karim S., Ribeiro J. M. (2015). An insight into the sialome of the lone star tick, amblyomma americanum, with a glimpse on its time dependent gene expression. PubMed DOI PMC

Kazimirova M., Stibraniova I. (2013). Tick salivary compounds: their role in modulation of host defences and pathogen transmission. PubMed DOI PMC

Kazimirova M., Thangamani S., Bartikova P., Hermance M., Holikova V., Stibraniova I., et al. (2017). Tick-borne viruses and biological processes at the tick-host-virus interface. PubMed DOI PMC

Keller P. M., Waxman L., Arnold B. A., Schultz L. D., Condra C., Connolly T. M. (1993). Cloning of the cDNA and expression of moubatin, an inhibitor of platelet aggregation. PubMed

Kim T. K., Tirloni L., Pinto A. F., Moresco J., Yates J. R., III, Da Silva Vaz I., et al. (2016). Ixodes scapularis tick saliva proteins sequentially secreted every 24 h during blood feeding. PubMed DOI PMC

Kotal J., Langhansova H., Lieskovska J., Andersen J. F., Francischetti I. M., Chavakis T., et al. (2015). Modulation of host immunity by tick saliva. PubMed DOI PMC

Kuhn N., Schmidt C. Q., Schlapschy M., Skerra A. (2016). PASylated coversin, a C5-Specific complement inhibitor with extended pharmacokinetics, shows enhanced anti-hemolytic activity in vitro. PubMed DOI

Li F. S., Weng J. K. (2017). Demystifying traditional herbal medicine with modern approach. PubMed DOI

Lieskovska J., Palenikova J., Sirmarova J., Elsterova J., Kotsyfakis M., Campos Chagas A., et al. (2015). Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells. PubMed DOI

Lung O., Tram U., Finnerty C. M., Eipper-Mains M. A., Kalb J. M., Wolfner M. F. (2002). The Drosophila melanogaster seminal fluid protein Acp62F is a protease inhibitor that is toxic upon ectopic expression. PubMed PMC

Mans B. J., Andersen J. F., Schwan T. G., Ribeiro J. M. (2008a). Characterization of anti-hemostatic factors in the argasid, Argas monolakensis: implications for the evolution of blood-feeding in the soft tick family. PubMed DOI PMC

Mans B. J., Ribeiro J. M., Andersen J. F. (2008b). Structure, function, and evolution of biogenic amine-binding proteins in soft ticks. PubMed DOI PMC

Mans B. J., Louw A. I., Neitz A. W. (2002a). Disaggregation of aggregated platelets by savignygrin, a alphaIIbeta3 antagonist from PubMed

Mans B. J., Louw A. I., Neitz A. W. (2002b). Savignygrin, a platelet aggregation inhibitor from the soft tick PubMed DOI

Mans B. J., Ribeiro J. M. (2008). Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins. PubMed DOI PMC

Marcet-Palacios M., Ewen C., Pittman E., Duggan B., Carmine-Simmen K., Fahlman R. P., et al. (2015). Design and characterization of a novel human Granzyme B inhibitor. PubMed DOI

Marchal C., Schramm F., Kern A., Luft B. J., Yang X., Schuijt T. J., et al. (2011). Antialarmin effect of tick saliva during the transmission of Lyme disease. PubMed DOI PMC

Mignogna G., Pascarella S., Wechselberger C., Hinterleitner C., Mollay C., Amiconi G., et al. (1996). BSTI, a trypsin inhibitor from skin secretions of Bombina bombina related to protease inhibitors of nematodes. PubMed DOI PMC

Montecucco F., Lenglet S., Braunersreuther V., Pelli G., Pellieux C., Montessuit C., et al. (2010). Single administration of the CXC chemokine-binding protein Evasin-3 during ischemia prevents myocardial reperfusion injury in mice. PubMed DOI

Montecucco F., Mach F., Lenglet S., Vonlaufen A., Gomes Quindere A. L., Pelli G., et al. (2014). Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis. PubMed DOI

Mudenda L., Pierle S. A., Turse J. E., Scoles G. A., Purvine S. O., Nicora C. D., et al. (2014). Proteomics informed by transcriptomics identifies novel secreted proteins in PubMed DOI

Narasimhan S., Koski R. A., Beaulieu B., Anderson J. F., Ramamoorthi N., Kantor F., et al. (2002). A novel family of anticoagulants from the saliva of Ixodes scapularis. PubMed DOI

Narasimhan S., Montgomery R. R., Deponte K., Tschudi C., Marcantonio N., Anderson J. F., et al. (2004). Disruption of Ixodes scapularis anticoagulation by using RNA interference. PubMed DOI PMC

Neelakanta G., Sultana H. (2015). Transmission-blocking vaccines: focus on anti-vector vaccines against tick-borne diseases. PubMed DOI PMC

Nunn M. A. (2004).

Nunn M. A., Sharma A., Paesen G. C., Adamson S., Lissina O., Willis A. C., et al. (2005). Complement inhibitor of C5 activation from the soft tick PubMed DOI

Nuttall P. A., Labuda M. (2004). Tick-host interactions: saliva-activated transmission. PubMed

Nuttall P. A., Labuda M. (2008). “Saliva-assisted transmission of tick-borne pathogens,” in DOI

Nuttall P. A., Paesen G. C. (2000).

Oleaga A., Escudero-Poblacion A., Camafeita E., Perez-Sanchez R. (2007). A proteomic approach to the identification of salivary proteins from the argasid ticks PubMed DOI

Oliveira C. J., Anatriello E., De Miranda-Santos I. K., Francischetti I. M., Sa-Nunes A., Ferreira B. R., et al. (2013). Proteome of PubMed DOI PMC

Paesen G. C., Adams P. L., Harlos K., Nuttall P. A., Stuart D. I. (1999). Tick histamine-binding proteins: isolation, cloning, and three-dimensional structure. PubMed DOI

Parizi L. F., Ali A., Tirloni L., Oldiges D. P., Sabadin G. A., Coutinho M. L., et al. (2018). Peptidase inhibitors in tick physiology. PubMed DOI

Paul S. M., Mytelka D. S., Dunwiddie C. T., Persinger C. C., Munos B. H., Lindborg S. R., et al. (2010). How to improve R&D productivity: the pharmaceutical industry’s grand challenge. PubMed

Paveglio S. A., Allard J., Mayette J., Whittaker L. A., Juncadella I., Anguita J., et al. (2007). The tick salivary protein, Salp15, inhibits the development of experimental asthma. PubMed DOI PMC

Pischke S. E., Gustavsen A., Orrem H. L., Egge K. H., Courivaud F., Fontenelle H., et al. (2017). Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function. PubMed DOI PMC

Porter L. M., Radulovic Z. M., Mulenga A. (2017). A repertoire of protease inhibitor families in PubMed DOI PMC

Pospisilova T., Urbanova V., Hes O., Kopacek P., Hajdusek O., Sima R. (2019). Tracking of Borrelia afzelii transmission from infected Ixodes ricinus nymphs to mice. PubMed DOI PMC

Preston S. G., Majtan J., Kouremenou C., Rysnik O., Burger L. F., Cabezas Cruz A., et al. (2013). Novel immunomodulators from hard ticks selectively reprogramme human dendritic cell responses. PubMed DOI PMC

Ramamoorthi N., Narasimhan S., Pal U., Bao F., Yang X. F., Fish D., et al. (2005). The Lyme disease agent exploits a tick protein to infect the mammalian host. PubMed DOI PMC

Ratcliffe N., Azambuja P., Mello C. B. (2014). Recent advances in developing insect natural products as potential modern day medicines. PubMed DOI PMC

Ribeiro J. M., Francischetti I. M. (2003). Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. PubMed DOI

Ribeiro J. M., Makoul G. T., Levine J., Robinson D. R., Spielman A. (1985). Antihemostatic, antiinflammatory, and immunosuppressive properties of the saliva of a tick, PubMed DOI PMC

Ribeiro J. M., Slovak M., Francischetti I. M. (2017). An insight into the sialome of PubMed DOI PMC

Romay-Penabad Z., Carrera Marin A. L., Willis R., Weston-Davies W., Machin S., Cohen H., et al. (2014). Complement C5-inhibitor rEV576 (coversin) ameliorates in-vivo effects of antiphospholipid antibodies. PubMed DOI

Roversi P., Johnson S., Preston S. G., Nunn M. A., Paesen G. C., Austyn J. M., et al. (2017). Structural basis of cholesterol binding by a novel clade of dendritic cell modulators from ticks. PubMed DOI PMC

Russo R. C., Alessandri A. L., Garcia C. C., Cordeiro B. F., Pinho V., Cassali G. D., et al. (2011). Therapeutic effects of evasin-1, a chemokine binding protein, in bleomycin-induced pulmonary fibrosis. PubMed DOI

Ryffel B., Couillin I., Maillet I., Schnyder B., Paesen G. C., Nuttall P., et al. (2005). Histamine scavenging attenuates endotoxin-induced acute lung injury. PubMed DOI

Sangamnatdej S., Paesen G. C., Slovak M., Nuttall P. A. (2002). A high affinity serotonin- and histamine-binding lipocalin from tick saliva. PubMed DOI

Schlapschy M., Binder U., Borger C., Theobald I., Wachinger K., Kisling S., et al. (2013). PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins. PubMed DOI PMC

Schuijt T. J., Coumou J., Narasimhan S., Dai J., Deponte K., Wouters D., et al. (2011a). A tick mannose-binding lectin inhibitor interferes with the vertebrate complement cascade to enhance transmission of the lyme disease agent. PubMed DOI PMC

Schuijt T. J., Narasimhan S., Daffre S., Deponte K., Hovius J. W., Van’t Veer C., et al. (2011b). Identification and characterization of PubMed DOI PMC

Schwarz A., Cabezas-Cruz A., Kopecky J., Valdes J. J. (2014). Understanding the evolutionary structural variability and target specificity of tick salivary Kunitz peptides using next generation transcriptome data. PubMed DOI PMC

Schwarz A., Valdes J. J., Kotsyfakis M. (2012). The role of cystatins in tick physiology and blood feeding. PubMed DOI PMC

Schwarz A., Von Reumont B. M., Erhart J., Chagas A. C., Ribeiro J. M., Kotsyfakis M. (2013). De novo Ixodes ricinus salivary gland transcriptome analysis using two next-generation sequencing methodologies. PubMed DOI PMC

Shim J. S., Liu J. O. (2014). Recent advances in drug repositioning for the discovery of new anticancer drugs. PubMed DOI PMC

Silverman G. A., Whisstock J. C., Bottomley S. P., Huntington J. A., Kaiserman D., Luke C. J., et al. (2010). Serpins flex their muscle: I. Putting the clamps on proteolysis in diverse biological systems. PubMed DOI PMC

Simo L., Kazimirova M., Richardson J., Bonnet S. I. (2017). The essential role of tick salivary glands and saliva in tick feeding and pathogen transmission. PubMed DOI PMC

Soltys J., Kusner L. L., Young A., Richmonds C., Hatala D., Gong B., et al. (2009). Novel complement inhibitor limits severity of experimentally myasthenia gravis. PubMed DOI PMC

Song Y., Gong K., Yan H., Hong W., Wang L., Wu Y., et al. (2014). Sj7170, a unique dual-function peptide with a specific alpha-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. PubMed DOI PMC

Stassens P., Bergum P. W., Gansemans Y., Jespers L., Laroche Y., Huang S., et al. (1996). Anticoagulant repertoire of the hookworm PubMed DOI PMC

Swanson S. J., Neitzel D., Reed K. D., Belongia E. A. (2006). Coinfections acquired from ixodes ticks. PubMed DOI PMC

Tang J., Fang Y., Han Y., Bai X., Yan X., Zhang Y., et al. (2015). YY-39, a tick anti-thrombosis peptide containing RGD domain. PubMed DOI

Tirloni L., Islam M. S., Kim T. K., Diedrich J. K., Yates J. R., III, Pinto A. F., et al. (2015). Saliva from nymph and adult females of PubMed DOI PMC

Tirloni L., Kim T. K., Pinto A. F. M., Yates J. R., III, Da Silva Vaz I., Jr., et al. (2017). Tick-host range adaptation: changes in protein profiles in unfed adult PubMed DOI PMC

Tirloni L., Reck J., Terra R. M., Martins J. R., Mulenga A., Sherman N. E., et al. (2014). Proteomic analysis of cattle tick PubMed DOI PMC

Tomas-Cortazar J., Martin-Ruiz I., Barriales D., Pascual-Itoiz M. A., De Juan V. G., Caro-Maldonado A., et al. (2017). The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant. PubMed DOI PMC

Tuppurainen E. S., Stoltsz W. H., Troskie M., Wallace D. B., Oura C. A., Mellor P. S., et al. (2011). A potential role for ixodid (hard) tick vectors in the transmission of lumpy skin disease virus in cattle. PubMed DOI

Valenzuela J. G., Francischetti I. M., Pham V. M., Garfield M. K., Mather T. N., Ribeiro J. M. (2002). Exploring the sialome of the tick PubMed

Veronese F. M., Mero A. (2008). The impact of PEGylation on biological therapies. PubMed DOI

Vieira A. T., Fagundes C. T., Alessandri A. L., Castor M. G., Guabiraba R., Borges V. O., et al. (2009). Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis. PubMed DOI PMC

Wagemakers A., Coumou J., Schuijt T. J., Oei A., Nijhof A. M., Van ’t Veer C., et al. (2016). An PubMed DOI

Wang X., Coons L. B., Taylor D. B., Stevens S. E., Jr., Gartner T. K. (1996). Variabilin, a novel RGD-containing antagonist of glycoprotein IIb-IIIa and platelet aggregation inhibitor from the hard tick PubMed DOI

Wang X., Huang Y., Niu S. B., Jiang B. G., Jia N., Van Der Geest L., et al. (2014). Genetic diversity of Salp15 in the Ixodes ricinus complex (Acari: Ixodidae). PubMed DOI PMC

Wang X. J., Ren J. L., Zhang A. H., Sun H., Yan G. L., Han Y., et al. (2019). Novel applications of mass spectrometry-based metabolomics in herbal medicines and its active ingredients: current evidence. PubMed

Wang Y., Li Z., Zhou Y., Cao J., Zhang H., Gong H., et al. (2016). Specific histamine binding activity of a new lipocalin from PubMed DOI PMC

Weston-Davies W., Couillin I., Schnyder S., Schnyder B., Moser R., Lissina O., et al. (2005). Arthropod-derived protein EV131 inhibits histamine action and allergic asthma. PubMed DOI

Whisstock J. C., Silverman G. A., Bird P. I., Bottomley S. P., Kaiserman D., Luke C. J., et al. (2010). Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions. PubMed DOI PMC

Wikel S. (2013). Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment. PubMed DOI PMC

Wikel S. K. (1982). Influence of Dermacentor andersoni infestation on lymphocyte responsiveness to mitogens. PubMed DOI

Xu X. L., Cheng T. Y., Yang H., Yan F., Yang Y. (2015). De novo sequencing, assembly and analysis of salivary gland transcriptome of PubMed DOI

Yu X., Gong H., Zhou Y., Zhang H., Cao J., Zhou J. (2015). Differential sialotranscriptomes of unfed and fed PubMed DOI PMC

Zhou W., Wang Y., Lu A., Zhang G. (2016). Systems pharmacology in small molecular drug discovery. PubMed DOI PMC

Zhou Y. F., Eng E. T., Zhu J., Lu C., Walz T., Springer T. A. (2012). Sequence and structure relationships within von Willebrand factor. PubMed DOI PMC

Tick cysteine protease inhibitors suppress immune responses in mannan-induced psoriasis-like inflammation

Iripin-1, a new anti-inflammatory tick serpin, inhibits leukocyte recruitment in vivo while altering the levels of chemokines and adhesion molecules

Serpins in Tick Physiology and Tick-Host Interaction

Lyme disease transmission by severely impaired ticks

rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii

Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine

Iripin-3, a New Salivary Protein Isolated From Ixodes ricinus Ticks, Displays Immunomodulatory and Anti-Hemostatic Properties In Vitro

A combined transcriptomic approach to identify candidates for an anti-tick vaccine blocking B. afzelii transmission

Tick Salivary Compounds for Targeted Immunomodulatory Therapy