Cyproheptadine hydrochloride inhibits African swine fever viral replication in vitro. (February 2023)

• Record Type: Journal Article
• Authors: Cui, Huimei; Yang, Jinke; Yang, Bo; Hao, Yu; Shi, Xijuan; Zhang, Dajun; Yang, Xing; Zhang, Ting; Zhao, DengShuai; Yuan, Xingguo; Chen, Xuehui; Liu, Xiangtao; Zheng, Haixue; Zhang, Keshan
• Is Part Of: Microbial pathogenesis. Volume 175(2023)
• Publication Date: 2023-02
• Subjects: Periactin -- African swine fever virus -- Replication inhibition -- Antiviral affect; ASFV African swine fever virus -- FBS fetal bovine serum -- MOI multiplicity of infection -- PAM porcine alveolar macrophage; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105957
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: African swine fever (ASF) is an infectious disease caused by the African swine fever virus (ASFV), and has a high mortality rate. It has caused serious socioeconomic consequences worldwide. Currently, there are no available commercial vaccines or antiviral drug interventions. D1133L is one of the key genes for ASFV replication and antiviral drug screening. In this study, a virtual screening software program, PyRx, was used to screen libraries of compounds against the potential drug target D1133L. Twelve compounds with a high affinity for ASFV D1133L were screened, and cyproheptadine hydrochloride (periactin) was identified as a candidate drug. The periactin has little cytotoxicity, and which dose-dependently inhibited ASFV replication in vitro . Further research indicated that periactin could significantly down-regulate D1133L at the transcriptional and protein levels with RT-qPCR and western blot methods. This study has provided important candidate drugs for the prevention and treatment of ASF, as well as biological materials and new fields of view for the research and development of vaccines and drugs for ASFV. Highlights: This study predicted the tertiary structure of ASFV D1133L, docked with 3206 FDA approved small molecule drugs in ZINC database, counted the binding energy of them, and screened 12 small molecules with binding energy ≥11.0 kcal/mol for antiviral activity verification based on cell level. It is proved that small molecule compound Periactin significantly inhibited the replication of ASFV in BMDMs. It is proved that small molecule compound Periactin could significantly inhibit the transcription and expression of D1133L which are important for ASFV replication. It is proved that the small molecule compound periactin has less cytotoxicity.