Application of inhibitors targeting EIF2AK2 protein in the preparation of drugs for preventing and / or treating pregnancy loss
By targeting the EIF2AK2 protein inhibitor C16, the problem of pregnancy loss caused by inflammatory disorders at the maternal-fetal interface and trophoblast cell death was solved, achieving safe and effective prevention and treatment of pregnancy loss.
Patent Information
- Application Number
- CN202310817747.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-05
- Publication Date
- 2025-09-19
- Estimated Expiration
- 2043-07-05
AI Technical Summary
Currently, there is no effective drug to prevent and treat pregnancy loss caused by inflammatory disorders at the maternal-fetal interface and trophoblast cell death, especially pregnancy loss caused by viral infection.
Inhibitors targeting the EIF2AK2 protein, especially the imidazole PKR inhibitor C16 (C16), are administered by intraperitoneal injection to inhibit the function of the EIF2AK2 protein and prevent the inflammatory response at the maternal-fetal interface and trophoblast cell death caused by interferon disorder.
It significantly inhibits pregnancy loss caused by type I interferon disorder, provides a safe and efficient means of prevention and treatment, protects the balance of the immune microenvironment at the maternal-fetal interface, and prevents the occurrence of adverse pregnancies.
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Figure CN116850184B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of medical technology, and in particular to use of an inhibitor targeting EIF2AK2 protein in the preparation of a drug for preventing and / or treating pregnancy loss. Background Art
[0002] Double-stranded RNA-dependent protein kinase (EIF2AK2) is an interferon-induced gene. Interferon-sensitive cells can induce the production of EIF2AK2 protein after interferon treatment. Studies have found that EIF2AK2 can play a role in antiviral, translation regulation, necroptosis and other biological functions. Imidazole oxygen indole PKR inhibitor C16 (PKR-IN-C16, molecular formula: C 13 H8N4OS (hereinafter referred to as C16) is a specific inhibitor of double-stranded RNA-dependent protein kinase (EIF2AK2). It effectively inhibits EIF2AK2 function, preventing EIF2AK2-induced neuronal damage and inhibiting inflammatory responses. Previous studies have also found that C16 can inhibit liver tumor growth.
[0003] Pregnancy loss occurs when the embryo itself fails to survive, and in some ways, it's considered pathological. Inflammatory disorders and barrier damage at the maternal-fetal interface are key factors. Miscarriage not only affects pregnant women physically, such as bleeding and infection, but can also lead to adverse psychological consequences such as anxiety, depression, and post-traumatic stress disorder.
[0004] Cell death at the maternal-fetal interface is a normal physiological process, with the production of cytokines and cell debris in a dynamic balance with the cleanup functions of macrophages and other cells. However, if the mother is invaded by exogenous pathogens during pregnancy, this can trigger a series of cell necrosis and release inflammatory substances, leading to an inflammatory response. This can disrupt the immune microenvironment at the maternal-fetal interface. Furthermore, pathologies such as trophoblast necrosis can disrupt maternal-fetal barrier function and embryonic development, potentially leading to pregnancy loss.
[0005] Exploring the key mechanisms by which viral infection (or interferon) regulates the biological functions of trophoblasts and identifying precise intervention targets has become a key and hot topic in current research. However, effective drugs for preventing pregnancy loss have not yet been found.
[0006] Therefore, it is very necessary to develop a safe and effective drug that can prevent maternal pathogen invasion and lead to pregnancy loss. Summary of the Invention
[0007] The present invention aims to overcome the shortcomings of the prior art by providing the use of inhibitors targeting the EIF2AK2 protein in the preparation of medicaments for preventing and / or treating pregnancy loss. The present invention has discovered that inhibitors targeting the EIF2AK2 protein can address pregnancy loss caused by inflammatory disorders at the maternal-fetal interface and trophoblast cell death, providing a safe and effective new treatment for adverse pregnancy outcomes.
[0008] To achieve the above object, the technical solution adopted by the present invention is:
[0009] In a first aspect, the present invention provides use of an inhibitor targeting EIF2AK2 protein in the preparation of a medicament for preventing and / or treating pregnancy loss.
[0010] The present invention has discovered through research that inhibitors targeting EIF2AK2 protein can prevent and treat pregnancy loss.
[0011] From the results of the examples of the present invention, it can be seen that the dosage and method of administration of Poly (I: C) sodium salt according to the present invention led to embryo absorption in pregnant mice, indicating that the method of constructing a pregnant mouse model of type I interferon disorder of the present invention is effective and feasible.
[0012] This study, using intraperitoneal injections in model mice, found that C16, an inhibitor targeting the EIF2AK2 protein, can rescue pregnancy loss induced by poly(I:C). Furthermore, in vitro experiments revealed that C16, an inhibitor targeting the EIF2AK2 protein, can suppress cell death and phosphorylation of related molecules caused by excessive type I interferon. This discovery represents the first discovery that an inhibitor targeting the EIF2AK2 protein can prevent pregnancy loss caused by interferon deregulation and demonstrates high biosafety.
[0013] As a preferred embodiment of the use of the present invention, the pregnancy loss is pregnancy loss caused by (a) viral infection-induced inflammatory disorder at the maternal-fetal interface and / or (b) trophoblast cell death.
[0014] As a preferred embodiment of the application of the present invention, the (a) is interferon disorder caused by viral infection, which induces inflammatory disorder at the maternal-fetal interface.
[0015] As a preferred embodiment of the application of the present invention, the pregnancy loss is pregnancy loss caused by viral infection-induced inflammatory disorder at the maternal-fetal interface.
[0016] As a preferred embodiment of the application of the present invention, the pregnancy loss is caused by interferon disorder-induced inflammatory disorder at the maternal-fetal interface.
[0017] As a preferred embodiment of the use of the present invention, the pregnancy loss is pregnancy loss caused by trophoblast death.
[0018] As a preferred embodiment of the use of the present invention, the pregnancy loss is pregnancy loss caused by trophoblast death.
[0019] As a preferred embodiment of the application of the present invention, the inhibitor targeting EIF2AK2 protein includes PKR-IN-C16 (C16, molecular formula: C 13 H8N4OS), PKR-IN-C51 (C51, molecular formula: C 23 H 21 One or both of N5).
[0020] As a preferred embodiment of the application of the present invention, the inhibitor targeting EIF2AK2 protein includes PKR-IN-C16 (C16, molecular formula: C 13 H8N4OS).
[0021] In a second aspect, the present invention provides a drug for preventing and / or treating pregnancy loss, comprising an inhibitor targeting EIF2AK2 protein or a pharmaceutically acceptable salt thereof.
[0022] As a preferred embodiment of the drug of the present invention, the drug further comprises a pharmaceutically acceptable excipient or carrier.
[0023] As a preferred embodiment of the drug of the present invention, the drug is in the form of an injection, tablet or capsule.
[0024] As a preferred embodiment of the drug of the present invention, the inhibitor targeting EIF2AK2 protein includes PKR-IN-C16 (C16, molecular formula: C 13 H8N4OS), PKR-IN-C51 (C51, molecular formula: C 23 H 21 N5) or both.
[0025] As a preferred embodiment of the drug of the present invention, the inhibitor targeting EIF2AK2 protein includes PKR-IN-C16 (C16, molecular formula: C 13 H8N4OS).
[0026] Compared with the prior art, the present invention has the following beneficial effects:
[0027] Through cell experiments and animal experiments, the present invention discovered for the first time that an inhibitor targeting the EIF2AK2 protein can significantly inhibit pregnancy loss caused by maternal type I interferon disorder. The inhibitor can be used as a drug to prevent and / or treat pregnancy loss, providing a safe and efficient new treatment for adverse pregnancies. The present invention provides a new means for treating type I interferon disorder caused by maternal infection during pregnancy, especially viral infection, and expands the clinical application range of the inhibitor, providing a new direction for the study of the mechanism of action of the inhibitor. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 The results of the effects of different drug treatments on the body weight of pregnant mice in Example 1 of the present invention are shown, wherein a is the initial body weight percentage change curve of the Control+PBS group and the C16+PBS group on different days of drug treatment; b is the initial body weight percentage change curve of the Control+PBS group and the Control+Poly(I:C) group on different days of drug treatment; c is the initial body weight percentage change curve of the Control+Poly(I:C) group and the C16+Poly(I:C) group on different days of drug treatment;
[0029] Figure 2 The results of the effects of different dosing treatments on pregnancy loss in pregnant mice with type I interferon disorder in Example 2 of the present invention are shown, wherein a is a representative graph of embryo absorption of mice in each treatment group, b is a statistical graph of embryo absorption rate of mice in each treatment group, and c is a statistical graph of weight of offspring mice in each treatment group;
[0030] Figure 3 The cell viability of trophoblast cells treated with different concentrations of the inhibitor C16 targeting the EIF2AK2 protein in Example 3 of the present invention;
[0031] Figure 4 is the cell survival rate of trophoblast cells treated with different concentrations of the inhibitor C16 targeting the EIF2AK2 protein in Example 3 of the present invention;
[0032] Figure 5 These are the results of RIPK1 / RIPK3 / MLKL phosphorylation levels in trophoblast cells treated with different concentrations of the inhibitor C16 targeting the EIF2AK2 protein in Example 3 of the present invention; wherein a is the phosphorylation level result of p-MLKL and p-RIPK1, and b is the phosphorylation level result of MLKL, p-MLKL, RIPK1, p-RIPK1, RIPK3, and p-RIPK3; PKR is the EIF2AK2 protein, and GAPDH is the reference protein. DETAILED DESCRIPTION
[0033] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.
[0034] C57BL / 6J mice were purchased from Beijing Weitonglihua Laboratory Animal Technology Co., Ltd.;
[0035] C16(I9785-5MG, molecular formula: C 13 H8N4OS) and Polyinosinic-polycytidylic acidsodium salt [Poly (I:C) sodium salt] were purchased from Sigma;
[0036] 10× protein lysis buffer, p-MLKL antibody, GAPDH antibody and protease inhibitor cocktail were purchased from CST; interferon (IFNα) was purchased from Shenyang Sansheng Pharmaceutical Co., Ltd.
[0037] Unless otherwise specified, other materials and reagents used in the examples can be obtained from commercial sources.
[0038] Example 1 Effect of inhibitors targeting EIF2AK2 protein on the body weight of pregnant mice
[0039] 1. Test method
[0040] (1) Preparation of reagents
[0041] C16 was selected as an inhibitor targeting EIF2AK2 protein, and C16 was prepared into a storage solution with a concentration of 5 mg / mL; Poly(I:C) sodium salt was prepared into a storage solution with a concentration of 12.5 μg / μL; the concentration of the Poly(I:C) sodium salt working solution used was 200 ng / 100 μL.
[0042] The solvent of C16 stock solution is 5% (v:v) dimethyl sulfoxide (DMSO) solution (5% DMSO + sterile water).
[0043] The solvent of the poly(I:C) sodium salt working solution is sterile PBS.
[0044] (2) Mouse treatment
[0045] Female and male C57BL / 6J mice were caged together at a ratio of 2:3 the night before. The next morning, the toes of mice with vaginal plugs were clipped, marked with numbers and recorded as E0.5. Female mice with vaginal plugs were housed in separate cages and divided into four groups. The treatment methods of the four groups were as follows: The first group was treated with intraperitoneal injection of DMSO solution (5% DMSO + sterile water) once a day from E5.5 to E11.5, and the dosage volume was determined according to the weight of the mouse (the dosage was the volume of solution corresponding to 0.5 mg / kg C16 per mouse); 100 μL of PBS was administered by intraperitoneal injection on E12.5; and DMSO solution (5% DMSO + sterile water) was resumed daily from E13.5 to E16.5, and the dosage volume was determined according to the weight of the mouse (the dosage was the volume of solution corresponding to 0.5 mg / kg C16 per mouse); it was recorded as the Control+PBS group.
[0046] The second group was treated as follows: once a day from E5.5 to E11.5, the drug was intraperitoneally injected with DMSO solution (5% DMSO + sterile water), and the administration volume was determined according to the weight of the mouse (administered according to the volume of solution corresponding to the dosage of 0.5 mg / kg C16 per mouse); on E12.5, 100 μL of Poly (I: C) sodium salt working solution was administered by intraperitoneal injection, and each pregnant mouse was given 200 ng of Poly (I: C) sodium salt; from E13.5 to E16.5, daily administration of DMSO solution (5% DMSO + sterile water) was resumed, and the administration volume was determined according to the weight of the mouse (administered according to the volume of solution corresponding to the dosage of 0.5 mg / kg C16 per mouse); recorded as the Control+Poly (I: C) group.
[0047] The third group was administered with intraperitoneal injection once a day from E5.5 to E11.5. The drug was C16 storage solution with a concentration of 5 mg / ml, and each mouse was administered 0.5 mg / kg C16; 100 μL of PBS was administered intraperitoneally on E12.5; and daily administration of 0.5 mg / kg C16 was resumed from E13.5 to E16.5; this was recorded as the C16+PBS group.
[0048] The fourth group was administered with the following method: once daily intraperitoneal injection from E5.5 to E11.5, with C16 stock solution at a concentration of 5 mg / ml, and each mouse was administered 0.5 mg / kg C16; on E12.5, Poly(I:C) sodium salt working solution was administered intraperitoneally at 100 μL / mouse (Poly(I:C) sodium salt 200 ng / mouse); and from E13.5 to E16.5, daily C16 administration was resumed at 0.5 mg / kg; this group was designated as the C16+Poly(I:C) group.
[0049] The mice were weighed daily during the dosing period to assess the effect of the drug on their body weight. The percentage of initial body weight at different days of treatment was calculated based on the recorded body weight.
[0050] 2. Test results
[0051] The results of the effects of different drug treatments on the body weight of pregnant mice are as follows Figure 1 As shown, a is the initial body weight percentage change curve of the Control+PBS group and the C16+PBS group after drug treatment on different days; b is the initial body weight percentage change curve of the Control+PBS group and the Control+Poly(I:C) group after drug treatment on different days; c is the initial body weight percentage change curve of the Control+Poly(I:C) group and the C16+Poly(I:C) group after drug treatment on different days.
[0052] from Figure 1 It can be seen that the inhibitor C16 targeting the EIF2AK2 protein does not affect the weight of pregnant mice during pregnancy at a dose of 0.5 mg / kg (a); the administration of Poly(I:C) sodium salt significantly reduces the weight of pregnant mice during pregnancy, indicating that the administration of Poly(I:C) sodium salt leads to embryo absorption, indicating that the method of constructing a pregnant mouse model induced by type I interferon disorder by Poly(I:C) sodium salt of the present invention is effective and feasible (b); the inhibitor C16 targeting the EIF2AK2 protein can reverse the weight reduction of pregnant mice caused by the administration of Poly(I:C) sodium salt to a certain extent (c).
[0053] The present application conducted the same experiment using PKR-IN-C51 (C51) and found that C51 could also reverse the reduced body weight of pregnant mice induced by the administration of Poly(I:C) sodium salt to a certain extent.
[0054] Example 2 Effect of inhibitors targeting EIF2AK2 protein on pregnancy loss in pregnant mice caused by type I interferon disorder. The present invention constructs a pregnant mouse model with type I interferon disorder, administers the inhibitor C16 targeting EIF2AK2 protein to the pregnant mouse model with type I interferon disorder, euthanizes the pregnant mice at E17.5, and calculates the embryo absorption rate to study the effect of inhibitors targeting EIF2AK2 protein on pregnancy loss in pregnant mice with type I interferon disorder.
[0055] 1. Test method
[0056] (1) Preparation of reagents
[0057] Same as Example 1.
[0058] (2) Mouse treatment
[0059] Female and male C57BL / 6J mice were caged together at a ratio of 2:3 the night before. The next morning, the toes of mice with vaginal plugs were clipped, marked with numbers and recorded as E0.5. Female mice with vaginal plugs were housed in separate cages and divided into four groups. The treatment methods of the four groups were as follows: The first group was treated with intraperitoneal injection of DMSO solution (5% DMSO + sterile water) once a day from E5.5 to E11.5, and the dosage volume was determined according to the weight of the mouse (the dosage was the volume of solution corresponding to 0.5 mg / kg C16 per mouse); 100 μL of PBS was administered by intraperitoneal injection on E12.5; and DMSO solution (5% DMSO + sterile water) was resumed daily from E13.5 to E16.5, and the dosage volume was determined according to the weight of the mouse (the dosage was the volume of solution corresponding to 0.5 mg / kg C16 per mouse); it was recorded as the Control+PBS group.
[0060] The second group was treated as follows: once a day from E5.5 to E11.5, the drug was intraperitoneally injected with DMSO solution (5% DMSO + sterile water), and the administration volume was determined according to the weight of the mouse (administered according to the volume of solution corresponding to the dosage of 0.5 mg / kg C16 per mouse); on E12.5, 100 μL of Poly (I: C) sodium salt working solution was administered by intraperitoneal injection, and each pregnant mouse was given 200 ng of Poly (I: C) sodium salt; from E13.5 to E16.5, daily administration of DMSO solution (5% DMSO + sterile water) was resumed, and the administration volume was determined according to the weight of the mouse (administered according to the volume of solution corresponding to the dosage of 0.5 mg / kg C16 per mouse); recorded as the Control+Poly (I: C) group.
[0061] The third group was administered with intraperitoneal injection once a day from E5.5 to E11.5. The drug was C16 storage solution with a concentration of 5 mg / ml, and each mouse was administered 0.5 mg / kg C16; 100 μL of PBS was administered intraperitoneally on E12.5; and daily administration of 0.5 mg / kg C16 was resumed from E13.5 to E16.5; this was recorded as the C16+PBS group.
[0062] The fourth group was administered with the following method: once daily intraperitoneal injection from E5.5 to E11.5, with C16 stock solution at a concentration of 5 mg / ml, and each mouse was administered 0.5 mg / kg C16; on E12.5, Poly(I:C) sodium salt working solution was administered intraperitoneally at 100 μL / mouse (Poly(I:C) sodium salt 200 ng / mouse); and from E13.5 to E16.5, daily C16 administration was resumed at 0.5 mg / kg; this group was designated as the C16+Poly(I:C) group.
[0063] Mice were euthanized at E17.5, and fetuses (offspring mice) and placentas were dissected to determine embryonic absorption. Individual embryos and corresponding placentas were dissected and photographed. Placental and embryonic tissues were preserved in paraformaldehyde / liquid nitrogen solution.
[0064] 2. Test results
[0065] The results of different drug treatments on pregnancy loss in pregnant mice induced by type I interferon disorder are as follows Figure 2 As shown, a is a representative graph of embryo absorption of mice in each treatment group, b is a statistical graph of embryo absorption rate of mice in each treatment group, and c is a statistical graph of weight of offspring mice in each treatment group.
[0066] from Figure 2 It can be seen that the inhibitor C16 targeting the EIF2AK2 protein can effectively reverse the loss of mouse embryos under the condition of high expression of type I interferon mediated by Poly(I:C) sodium salt, while there is no significant difference in the weight of mouse embryos among the groups. This shows that the inhibitor C16 targeting the EIF2AK2 protein can significantly reverse the pregnancy loss induced by type I interferon disorder in pregnant mice without affecting the weight of the embryos.
[0067] The present application conducted the same experiment using PKR-IN-C51 (C51) and found that C51 can also significantly reverse pregnancy loss in pregnant mice induced by type I interferon disorder without affecting the weight of the embryos.
[0068] Example 3 Effects of Inhibitors Targeting EIF2AK2 Protein on Excessive Type I Interferon-Regulated Trophoblast Activity and Signaling Pathways
[0069] 1. Effects of the EIF2AK2 inhibitor C16 on the biological activity of trophoblast cells
[0070] (1) Test method
[0071] The extravillous trophoblast cell line HTR8 / Svneo cells (purchased from ATCC) were plated in 6-well plates. The cell culture medium was RPMI-1640 medium containing 10% FBS (i.e., RPMI-1640 complete medium). The next day, the medium was replaced with RPMI-1640 complete medium containing the EIF2AK2 protein inhibitor C16 (the final concentrations of C16 were 0uM, 0.1uM, 0.2uM, 0.5uM, 1uM, and 2uM, respectively; prepared using a C16 working solution with a concentration of 10μg / 100μL) and treated for 48h. The cell viability was detected using a CCK8 kit (purchased from MCE) according to the instructions.
[0072] (2) Test results
[0073] The cell viability of trophoblast cells treated with different concentrations of the inhibitor C16 targeting EIF2AK2 protein is shown in Figure 3. Figure 3 shown.
[0074] from Figure 3 It can be seen that the inhibitor C16 targeting EIF2AK2 protein has little effect on the activity of trophoblast cells when the final concentration is 0.2uM or 0.5uM and the cells are treated for 48 hours.
[0075] 2. Effects of the inhibitor C16 targeting EIF2AK2 protein on the biological activity of trophoblasts regulated by excessive interferon (1) Experimental methods
[0076] ① Extravillous trophoblast cell line HTR8 / Svneo cells (purchased from ATCC) were plated in 6-well plates. The cell culture medium was RPMI-1640 medium containing 10% FBS (i.e., RPMI-1640 complete medium). The next day, the RPMI-1640 complete medium was replaced with the EIF2AK2 protein inhibitor C16 (final concentrations of C16 were 0uM, 0.2uM, and 0.5uM, respectively).
[0077] ② After 6 hours of C16 pretreatment, 3000 U of interferon (IFNα) was given for 48 hours;
[0078] ③Use trypan blue staining to detect cell death and calculate the cell survival rate.
[0079] (2) Test results
[0080] The cell survival rate of trophoblast cells treated with different concentrations of inhibitor C16 targeting EIF2AK2 protein is shown in Figure 3. Figure 4 shown.
[0081] from Figure 4 It can be seen that the inhibitor C16 targeting EIF2AK2 protein can reverse the trophoblast cell death caused by type I interferon at a concentration of 0.2uM.
[0082] 3. Effects of the EIF2AK2 inhibitor C16 on p-MLKL and other signaling pathways in trophoblasts (1) Experimental methods
[0083] ① Extravillous trophoblast cell line HTR8 / Svneo cells (purchased from ATCC) were cultured in 6-well plates in RPMI-1640 medium containing 10% FBS (i.e., RPMI-1640 complete medium). The next day, the RPMI-1640 complete medium was replaced with the EIF2AK2 protein inhibitor C16 (final concentrations of C16 were 0uM, 0.2uM, and 0.5uM, respectively).
[0084] ② After 6 hours of C16 pretreatment, 3000 U of interferon (IFNα) was given for 48 hours;
[0085] ③ Cell proteins were extracted and Western blot was performed using 10× protein lysis buffer, p-MLKL antibody, GAPDH antibody, and protease inhibitor cocktail to detect the phosphorylation levels of MLKL, p-MLKL, RIPK1, p-RIPK1, RIPK3, and p-RIPK3.
[0086] (2) Test results
[0087] The results of RIPK1 / RIPK3 / MLKL phosphorylation levels in trophoblasts treated with different concentrations of the inhibitor C16 targeting EIF2AK2 protein are as follows: Figure 5 As shown; a is the phosphorylation level results of p-MLKL and p-RIPK1, b is the phosphorylation level results of MLKL, p-MLKL, RIPK1, p-RIPK1, RIPK3, and p-RIPK3; PKR is the EIF2AK2 protein, and GAPDH is the reference protein.
[0088] from Figure 5 It can be seen that the inhibitor C16 targeting EIF2AK2 protein in trophoblast cells can inhibit the phosphorylation level of p-MLKL, a key molecule of type I interferon-mediated necroptosis (a). At the same time, C16 can also significantly inhibit the phosphorylation of key programmed necrosis molecules MLKL, RIPK1, and RIPK3 (b).
[0089] This application used PKR-IN-C51 (C51) to conduct the same experiment and found that C51 can also inhibit the phosphorylation of p-MLKL, a key molecule of type I interferon-mediated necroptosis; and inhibit the phosphorylation of key programmed necrosis molecules MLKL, RIPK1, and RIPK3.
[0090] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.
Claims
1. Use of an inhibitor targeting EIF2AK2 protein in the preparation of a drug for preventing and / or treating pregnancy loss, characterized in that: The pregnancy loss is caused by (a) viral infection-induced inflammatory disorders at the maternal-fetal interface and (b) trophoblast cell death; The inhibitor targeting EIF2AK2 protein is PKR-IN-C51.
2. Use of an inhibitor targeting EIF2AK2 protein in the preparation of a drug for preventing and / or treating pregnancy loss, characterized in that: The pregnancy loss is (a) pregnancy loss caused by viral infection-induced inflammatory disorder at the maternal-fetal interface; the inhibitor targeting EIF2AK2 protein is PKR-IN-C51.
3. The use according to claim 1 or 2, characterized in that The aforementioned (a) is interferon disorder caused by viral infection, which induces inflammatory disorder at the maternal-fetal interface.