CN-121991864-A - Streptomyces LM-35, metabolite thereof and application thereof in preparation of medicines for treating or preventing porcine reproductive and respiratory syndrome virus infection

Abstract

The invention belongs to the technical field of livestock and poultry antiviral drugs, and discloses streptomycete LM-35, a metabolite thereof and application of the streptomycete LM-35 in preparation of drugs for treating or preventing porcine reproductive and respiratory syndrome virus infection. Anti-infection studies of PRRSV at both cellular and animal body levels were performed with fermentation supernatants of streptomyces LM-35, which were found to have significant anti-PRRSV activity both in vivo and in vitro. The pig survival rate of feeding the group containing the streptomycete LM-35 fermentation liquor reaches 80%, the adverse effect of PRRSV infection on the body can be effectively controlled, and the method can be used for preventing and controlling PRRSV.

Inventors

• JIN MEILIN
• LI XIN
• WANG QINGXIU
• WANG TIANLIANG
• LI YAQIN
• LI YANG
• SUN XIAOMEI
• ZHONG MING
• YANG LI
• Cheng Chuxing
• ZOU ZHONG
• KANG CHAO

Assignees

• 华中农业大学
• 武汉科缘生物发展有限责任公司
• 湖北江夏实验室

Dates

Publication Date

20260508

Application Date

20260410

Claims (7)

1. 1. An isolated Streptomyces spp LM-35, said Streptomyces spp having a preservation number of CCTCC NO: M2026442.
2. 2. The fermentation supernatant of Streptomyces LM-35 according to claim 1.
3. 3. The fermentation supernatant according to claim 2, wherein one of the active ingredients is 4-methylcatechol.
4. 4. A complex whose active ingredient comprises streptomyces LM-35 according to claim 1 and/or a fermentation supernatant according to claim 2.
5. 5. Use of streptomyces LM-35 according to claim 1, a fermentation supernatant according to claim 2 and/or a complex according to claim 4 for the preparation of a medicament for the treatment or prevention of porcine reproductive and respiratory syndrome virus infection.
6. 6. Use of streptomyces LM-35 according to claim 1, a fermentation supernatant according to claim 2 and/or a complex according to claim 4 for the preparation of a vaccine for porcine reproductive and respiratory syndrome.
7. 7. Use of streptomyces LM-35 according to claim 1, a fermentation supernatant according to claim 2 and/or a compound according to claim 4 for the preparation of a pig feed additive.

Description

Streptomyces LM-35, metabolite thereof and application thereof in preparation of medicines for treating or preventing porcine reproductive and respiratory syndrome virus infection Technical Field The invention belongs to the technical field of livestock and poultry antiviral microecological preparations, and in particular relates to streptomycete LM-35, a metabolite thereof and application of the streptomycete LM-35 in preparation of a medicament for treating or preventing porcine reproductive and respiratory syndrome virus infection. Background Porcine reproductive and respiratory syndrome (Porcine Reproductive and Respiratory Syndrome, PRRS) is a highly contagious disease caused by Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and its typical clinical characteristics include reproductive disorders (e.g., abortion, stillbirth, weaning) in pregnant sows and respiratory symptoms (e.g., coughing, dyspnea, pneumonia) in pigs of all ages. The PRRSV induces persistent immunosuppression by targeting critical immune cells such as infected alveolar macrophages, thereby obviously increasing the risk of co-infection of secondary bacteria or viruses, and the virus has extremely high gene variation rate (especially ORF5 and Nsp2 gene regions), so that the existing commercial vaccine strain has low antigen matching degree with epidemic wild strain and limited cross protection efficacy. Therefore, there is a need to develop novel prevention and control strategies with broad-spectrum antiviral activity, novel mechanism of action, and less susceptibility to drug resistance. Streptomyces spp is used as a representative genus with the most abundant secondary metabolites in actinomycetes, and can synthesize natural compounds (such as macrolides, ansamycins and nucleoside derivatives) with various structures and wide biological activities, wherein part of metabolites have proven to have the potential of regulating host innate immune response or directly inhibiting virus replication, and important resources and new paths are provided for the research and development of original antiviral drugs targeting PRRSV. Related studies have shown that secondary metabolites produced by streptomyces exert antiviral effects through multiple mechanisms, including direct disruption of viral particle structural integrity, targeted inhibition of viral replication key links (e.g., genome replication, protein translation, and viral assembly), and bidirectional regulation of host innate and adaptive immune responses. Taking orchid Du Lian mould (Streptomyces lavendulae) as an example, the compound can efficiently synthesize 1-deoxynojirimycin (1-deoxynojirimycin, DNJ) under specific solid state fermentation conditions, and blocks N-linked glycosylation modification of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) envelope glycoprotein GP5 by specifically inhibiting host alpha-glucosidase I/II activity, so that GP5 space conformation is abnormal and maturation is blocked, fusion of a virus envelope and a host cell membrane is obviously inhibited, and virus invasion efficiency is reduced. Compared with the traditional chemically synthesized antiviral drugs, the active metabolite of streptomycete source has the comprehensive advantages of high natural structure diversity, novel action targets, excellent biocompatibility, low drug resistance risk and the like. In addition, the system optimizes key fermentation parameters such as carbon-nitrogen source proportion, inorganic salt concentration, pH gradient, dissolved oxygen level, induction time and the like, can obviously improve the titer and stability of a target active product, combines a genome excavation platform (such as ANTISMASH) to accurately predict and functionally annotate a secondary metabolism gene cluster, and is aided with heterologous expression and gene knockout verification, so that a potential antiviral biosynthesis pathway can be efficiently analyzed, and the discovery, structure confirmation and mechanism elucidation of a novel lead compound are accelerated. Therefore, the Streptomyces strain with strong and specific PRRSV resisting activity is screened and identified, which is not only helpful for expanding the antiviral natural product resource library, but also has important scientific value and application prospect for developing a safe and sustainable novel prevention and control strategy and alternative treatment means. The research is based on a high-throughput cytopathic effect (CPE) inhibition screening system, obtains streptomyces (transient No. LM-35) which shows remarkable inhibition activity on PRRSV replication, and is proved by quantitative analysis of ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), DNJ and other known inhibitors (such as castanospermine, swainsonine) for targeting GP5 glycosylation are not detected in the active metabolic spectrum, and the result breaks through the existing cognitive