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Volume 13
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10.3390/toxins13120913
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Article

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

by
Hajer Aounallah
1,2,
Melissa Regina Fessel
1,
Mauricio Barbugiani Goldfeder
1,
Eneas Carvalho
3,
Chaima Bensaoud
4,
Ana Marisa Chudzinski-Tavassi
1,5,
Ali Bouattour
2,
Youmna M’ghirbi
2,* and
Fernanda Faria
1,*
1
Innovation and Development Laboratory, Innovation and Development Center, Instituto Butantan, São Paulo 05503-900, Brazil
2
Laboratory of Viruses, Vectors and Hosts (LR20IPT02), Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia
3
Laboratory of Bacteriology, Butantan Institute, São Paulo 05503-900, Brazil
4
Institute of Parasitology, Biology Centre, Czech Academy of Sciences, 37005 Ceske Budejovice, Czech Republic
5
Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, Butantã, São Paulo 05503-900, Brazil
*
Authors to whom correspondence should be addressed.
Toxins 2021, 13(12), 913; https://doi.org/10.3390/toxins13120913
Submission received: 28 October 2021 / Revised: 1 December 2021 / Accepted: 8 December 2021 / Published: 20 December 2021
(This article belongs to the Special Issue Celebrating 120 Years of Butantan Institute Contributions for Toxinology)
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Abstract

Hemostatic disorders are caused either by platelet-related dysfunctions, defective blood coagulation, or by a combination of both, leading to an increased susceptibility to cardiovascular diseases (CVD) and other related illnesses. The unique specificity of anticoagulants from hematophagous arthropods, such as ticks, suggests that tick saliva holds great promise for discovering new treatments for these life-threatening diseases. In this study, we combined in silico and in vitro analyses to characterize the first recombinant serpin, herein called Dromaserpin, from the sialotranscriptome of the Hyalomma dromedarii tick. Our in silico data described Dromaserpin as a secreted protein of ~43 kDa with high similarities to previously characterized inhibitory serpins. The recombinant protein (rDromaserpin) was obtained as a well-structured monomer, which was tested using global blood coagulation and platelet aggregation assays. With this approach, we confirmed rDromaserpin anticoagulant activity as it significantly delayed plasma clotting in activated partial thromboplastin time and thrombin time assays. The profiling of proteolytic activity shows its capacity to inhibit thrombin in the micromolar range (0.2 to 1 μM) and in the presence of heparin this inhibition was clearly increased. It was also able to inhibit Kallikrein, FXIa and slightly FXIIa, with no significant effect on other factors. In addition, the rDromaserpin inhibited thrombin-induced platelet aggregation. Taken together, our data suggest that rDromaserpin deserves to be further investigated as a potential candidate for developing therapeutic compounds targeting disorders related to blood clotting and/or platelet aggregation.
Keywords: Hyalomma dromedarii; salivary glands; serpin; anticoagulants; thrombin inhibitor Hyalomma dromedarii; salivary glands; serpin; anticoagulants; thrombin inhibitor

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MDPI and ACS Style

Aounallah, H.; Fessel, M.R.; Goldfeder, M.B.; Carvalho, E.; Bensaoud, C.; Chudzinski-Tavassi, A.M.; Bouattour, A.; M’ghirbi, Y.; Faria, F. rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii. Toxins 2021, 13, 913. https://doi.org/10.3390/toxins13120913

AMA Style

Aounallah H, Fessel MR, Goldfeder MB, Carvalho E, Bensaoud C, Chudzinski-Tavassi AM, Bouattour A, M’ghirbi Y, Faria F. rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii. Toxins. 2021; 13(12):913. https://doi.org/10.3390/toxins13120913

Chicago/Turabian Style

Aounallah, Hajer, Melissa Regina Fessel, Mauricio Barbugiani Goldfeder, Eneas Carvalho, Chaima Bensaoud, Ana Marisa Chudzinski-Tavassi, Ali Bouattour, Youmna M’ghirbi, and Fernanda Faria. 2021. "rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii" Toxins 13, no. 12: 913. https://doi.org/10.3390/toxins13120913

APA Style

Aounallah, H., Fessel, M. R., Goldfeder, M. B., Carvalho, E., Bensaoud, C., Chudzinski-Tavassi, A. M., Bouattour, A., M’ghirbi, Y., & Faria, F. (2021). rDromaserpin: A Novel Anti-Hemostatic Serpin, from the Salivary Glands of the Hard Tick Hyalomma dromedarii. Toxins, 13(12), 913. https://doi.org/10.3390/toxins13120913

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