1. Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia 2. All-Russia Research Institute of Agricultural Biotechnology, Moscow, Russia 3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia
The aim of this study was to investigate the effects of Gloydius blomhoffii and Gloydius halys venoms and their fractions on platelet and plasma hemostasis, and to evaluate the ability of the sPLA2 inhibitor Varespladib to neutralize the coagulopathic activity mediated by secretory phospholipase A2 (sPLA2) present in these venoms. The proaggregatory effect of whole G. halys and G. blomhoffii venoms on platelet hemostasis was associated with multidirectional effects of their multiple protein components, while sPLA2-containing fractions exhibited an antiaggregatory effect. Whole G. halys and G. blomhoffii venoms and Varespladib added to them did not affect the extrinsic pathway of hemocoagulation, but inhibited the intrinsic pathway of human blood coagulation. The paradoxical effect of further enhancing the anticoagulant activity of G. halys and G. blomhoffii venoms with the sPLA2 inhibitor Varespladib could be determined by a stronger sPLA2 interaction with blood coagulation factor Xa after formation of the enzyme-inhibitor complex.
Solovyeva M.A., Galebskaya L.V., Galkin M.A., Berdichevskiy G.M., Semenova E.V., Mikhel I.M., Rogozhin E.A., Vasina L.V. (2026) The effect of the secretory phospholipases A2 from Gloydius blomhoffii and Gloydius halys venoms on hemostasis components in vitro. Biomeditsinskaya Khimiya, 72(1), 21-27.
Solovyeva M.A. et al. The effect of the secretory phospholipases A2 from Gloydius blomhoffii and Gloydius halys venoms on hemostasis components in vitro // Biomeditsinskaya Khimiya. - 2026. - V. 72. -N 1. - P. 21-27.
Solovyeva M.A. et al., "The effect of the secretory phospholipases A2 from Gloydius blomhoffii and Gloydius halys venoms on hemostasis components in vitro." Biomeditsinskaya Khimiya 72.1 (2026): 21-27.
Solovyeva, M. A., Galebskaya, L. V., Galkin, M. A., Berdichevskiy, G. M., Semenova, E. V., Mikhel, I. M., Rogozhin, E. A., Vasina, L. V. (2026). The effect of the secretory phospholipases A2 from Gloydius blomhoffii and Gloydius halys venoms on hemostasis components in vitro. Biomeditsinskaya Khimiya, 72(1), 21-27.
References
Oliveira A.L., Viegas M.F., da Silva S.L., Soares A.M., Ramos M.J., Fernandes P.A. (2022) The chemistry of snake venom and its medicinal potential. Nat. Rev. Chem., 6(7), 451–469. CrossRef Scholar google search
Hiu J.J., Yap M.K.K. (2020) Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and L-amino acid oxidase. Biochem. Soc. Trans., 48(2), 719–731. CrossRef Scholar google search
Bulfone T.C., Samuel S.P., Bickler P.E., Lewin M.R. (2018) Developing small molecule therapeutics for the initial and adjunctive treatment of snakebite. J. Trop. Med., 2018, 4320175. CrossRef Scholar google search
Gerardo C.J., Carter R.W., Kumar S., Shirazi F.M., Kotehal S.D., Akpunonu P.D., Bhalla A., Schwartz R.B., Bammigatti C., Manikath N., Mukherjee P.P., Arnold T.C., Wolk B.J., Sheikh S.S., Sollee D.R., Vearrier D.J., Francis S.J., Aizenberg A., Kumar H., Ravikumar M.K., Sarkar S., Haston T., Micciche A., Oomman S.C., Owen J.L., Ritter B.A., Samuel S.P., Lewin M.R., Platts-Mills T.F. (2024) Oral varespladib for the treatment of snakebite envenoming in India and the USA (BRAVO): a phase II randomised clinical trial. BMJ Glob. Health, 9(10), e015985. CrossRef Scholar google search
Xie C., Albulescu L-O., Still K.B.M., Slagboom J., Zhao Y., Jiang Z., Somsen G., Vonk F., Casewell N., Kool J. (2020) Varespladib inhibits the phospholipase A2 and coagulopathic activities of venom components from hemotoxic snakes. Biomedicines, 8(6), 165. CrossRef Scholar google search
Kazandjian T.D., Arrahman A., Still K.B.M., Somsen G.W., Vonk F.J., Casewell N.R., Wilkinson M., Kool J. (2021) Anticoagulant activity of Naja nigricollis venom is mediated by phospholipase A2 toxins and inhibited by varespladib. Toxins (Basel), 13(5), 302. CrossRef Scholar google search
Ha S.-J., Choi Y.-O., Kwag E.-B., Kim S.-D., Yoo H.-S., Kang I.-C., Park S.-J. (2022) Qualitative analysis of proteins in two snake venoms, Gloydius blomhoffii and Agkistrodon acutus. J. Pharmacopuncture, 25(1), 52–62. CrossRef Scholar google search
Li S., Wang J., Zhang X., Ren Y., Wang N., Zhao K., Chen X., Zhao C., Li X., Shao J., Yin J., West M.B., Xu N., Liu S. (2004) Proteomic characterization of two snake venoms: Naja naja atra and Agkistrodon halys. Biochem. J., 384(Pt 1), 119–127. CrossRef Scholar google search
Kini RM. (2005) Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms. Toxicon, 45(8), 1147–1161. CrossRef Scholar google search
Ullah A., Masood R., Ali I., Ullah K., Ali H., Akbar H., Betzel C. (2018) Thrombin-like enzymes from snake venom: structural characterization and mechanism of action. Int. J. Biol. Macromol., 114, 788–811. CrossRef Scholar google search
Castro H.C., Zingali R.B., Albuquerque M.G., Pujol-Luz M., Rodrigues C.R. (2004) Snake venom thrombin-like enzymes: from reptilase to now. Cell. Mol. Life Sci., 61(7–8), 843–856. CrossRef Scholar google search
Zeng F., Shen B., Zhu Z., Zhang P., Ji Y., Niu L., Li X., Teng M. (2013) Crystal structure and activating effect on RyRs of AhV TL-I, a glycosylated thrombin-like enzyme from Agkistrodon halys snake venom. Arch. Toxicol., 87(3), 535–545. CrossRef Scholar google search
Zhong X., Liu J., Wu X., Zhou Y. (2001) Expression, purification and biochemical characterization of a recombinant phospholipase A2 with anticoagulant activity from Agkistrodon halys Pallas. J. Nat. Toxins, 10(1), 17–25. Scholar google search
Faure G., Gowda V.T., Maroun R.C. (2007) Characterization of a human coagulation factor Xa-binding site on Viperidae snake venom phospholipases A2 by affinity binding studies and molecular bioinformatics. BMC Struct. Biol., 7, 82. CrossRef Scholar google search
Faure G., Saul F. (2011) Structural and functional characterization of anticoagulant, FXa-binding Viperidae snake venom phospholipases A2. Acta Chimica Slovenica, 58(4), 671–677. Scholar google search
Youngman N.J., Walker A., Naude A., Coster K., Sundman E., Fry B.G. (2020) Varespladib (LY315920) neutralises phospholipase A2 mediated prothrombinase-inhibition induced by Bitis snake venoms. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 236, 108818. CrossRef Scholar google search
Ivanušec A., Šribar J., Križaj I. (2022) Secreted phospholipases A2 — not just enzymes: revisited. Int. J. Biol. Sci., 18(2), 873–888. CrossRef Scholar google search