CN-122011210-A - Small-molecule short peptide K82-pe for resisting vascular remodeling caused by Zika virus and application thereof

CN122011210ACN 122011210 ACN122011210 ACN 122011210ACN-122011210-A

Abstract

The invention discloses a small molecule short peptide for resisting vascular remodeling caused by Zika virus and application thereof. The small molecule short peptide is formed by fusing cell membrane penetrating peptide and functional amino acid sequence, and the amino acid sequence is shown as SEQ ID NO. 1. The short peptide can be used for preparing medicines for preventing or treating vascular diseases induced by virus infection, especially for aortic intimal hyperplasia and phenotype conversion of vascular smooth muscle cells from contractile to synthetic. The short peptide can reduce the crotonylation modification level of MYH9 protein in vascular smooth muscle cells, promote the expression of alpha-smooth muscle actin and smooth muscle 22 alpha protein in vascular tissues, thereby improving vascular pathological injury caused by virus infection, reducing the thickness of blood vessels and increasing the medium membrane/intima ratio. The invention also provides a pharmaceutical composition containing the small molecule short peptide. The invention provides a new therapeutic strategy for preventing and treating vascular diseases related to virus infection.

Inventors

ZHENG CHANGBO
Gao Wencong
CHEN PENG
Wang Binbao
YU HEMIN
TAN JIAXIANG
YANG TIEHUA

Assignees

昆明医科大学

Dates

Publication Date: 20260512
Application Date: 20260210

Claims (10)

1. The small molecule short peptide for resisting vascular remodeling caused by Zika virus is characterized by being formed by fusing cell membrane penetrating peptide and functional amino acid sequence, wherein the amino acid sequence of the short peptide is shown as SEQ ID NO. 1.
2. Use of the small molecule short peptide of claim 1 in the manufacture of a medicament for the prevention or treatment of vascular disease induced by viral infection.
3. Use according to claim 2, wherein the vascular disease comprises aortic intimal hyperplasia and/or vascular smooth muscle cell transition from a contractile to a synthetic phenotype.
4. The use according to claim 2, wherein the medicament promotes the expression of alpha-smooth muscle actin and/or smooth muscle 22 alpha protein in vascular tissue.
5. The use according to claim 2, wherein the medicament reduces the level of crotonylation modification of MYH9 protein in vascular smooth muscle cells.
6. The use according to claim 2, wherein the medicament ameliorates vascular pathological lesions caused by viral infections.
7. The use according to any one of claims 2 to 8, wherein the medicament further comprises pharmaceutically acceptable excipients.
8. Use of the small molecule short peptide of claim 1 in the preparation of a formulation for reducing the level of crotonylation modification of a MYH9 protein.
9. Use of the small molecule short peptide of claim 1 for the preparation of a formulation for promoting expression of alpha-smooth muscle actin and/or smooth muscle 22 alpha protein.
10. A pharmaceutical composition comprising a therapeutically effective amount of the small molecule short peptide of claim 1 and a pharmaceutically acceptable adjuvant.

Description

Small-molecule short peptide K82-pe for resisting vascular remodeling caused by Zika virus and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a small molecule short peptide K82-pe for resisting vascular remodeling caused by Zika virus and application thereof. More particularly, the present invention relates to a small molecule short peptide capable of specifically reducing the crotonylation modification level of a non-muscle myosin heavy chain 9 (MYH 9) protein, and its use in the prevention or treatment of vascular diseases induced by ZIKV infection. Background Vascular remodeling (Vascular Remodeling) is a common pathological basis of various vascular diseases, and is essentially the structural and functional adaptability adjustment of the vascular wall to cope with internal and external environmental changes, and is specifically expressed by dynamic changes of the wall thickness, the lumen diameter and the vascular function, and the cooperative changes of vascular endothelial cells, smooth muscle cells, fibroblasts and extracellular matrix (ECM) are involved, so that the vascular remodeling (Vascular Remodeling) can be seen in normal physiological development (such as embryo angiogenesis and vascular adaptation after exercise), and is also often accompanied with various cardiovascular diseases such as hypertension, atherosclerosis, diabetic vascular lesions and the like, and is one of the key pathological links of disease progression. Vascular smooth muscle cells (Vascular Smooth Muscle Cells, VSMCs) as the major cellular component of arterial vessel walls undergo phenotypic transformation under pathological conditions, promoting proliferation and migration, which in turn leads to intimal hyperplasia, which has become a central pathological feature of vascular remodeling. Thus, intervention in the phenotypic switching of vascular smooth muscle cells is considered as a potential strategy to inhibit vascular remodeling. Vascular remodeling can be induced for a variety of reasons, and viral infection is one of the key causes of vascular remodeling, however, its exact pathophysiological mechanism is not yet fully understood. ZiKV is a single-stranded RNA virus wrapped by polyprotein, and has become a threat of global epidemic disease because of its rapid transmission rate and severe consequences such as neonatal cephalic deformity after infection. Although previous studies have shown that the zika virus is able to infect and damage cerebral, retinal and placental vessels of different animals, the effect of the zika virus infection on aortic damage, especially on vascular smooth muscle cell phenotype transformation and vascular intimal hyperplasia, is still unclear. At present, besides surgical intervention, there is no target drug capable of effectively treating vascular remodeling in clinic, and particularly, there is no target drug for virus-induced vascular injury. In view of the above, key molecular nodes for regulating and controlling vascular phenotype switching are discovered, and corresponding targeted treatment strategies are developed accordingly, so that the method has important clinical value and urgent application requirements. Recent studies have shown that non-muscle myosin heavy chain 9 (MYH 9) plays an important role in angiotensin II-induced hypertension vascular remodeling and atherosclerotic plaque formation as a key protein of cytoskeleton and contraction. In addition, bioinformatic analysis suggests that the MYH9 gene is involved in viral myocarditis-related pathways, and its proteins are also annotated as having potential viral receptor activity. At present, no research directly reveals the specific action mechanism of MYH9 in acute vascular injury and remodeling caused by specific virus infection (especially Zika virus infection), no report is paid attention to crotonylation (Kcr) modification of MYH9, and no medicine or biological preparation for treating viral vascular diseases by targeting MYH9 or crotonylation modification thereof is available. Disclosure of Invention The primary aim of the invention is to overcome the defects of the prior art and provide a small molecule short peptide with a brand new mechanism, which can enter cells with high efficiency and specifically reduce the crotonylation modification level of MYH9 protein. It is another object of the present invention to provide a novel use of the above small molecule short peptide for preparing a medicament for preventing or treating vascular remodeling diseases induced by Zika virus infection, particularly for treating aortic intimal hyperplasia and reversing pathological phenotype switching of vascular tissues after Zika virus infection. In order to achieve the above purpose, the invention adopts the following technical scheme: In a first aspect, the invention provides a small molecule short peptide, the amino acid sequence of which is shown in