Synthesized Magnolol Derivatives Improve Anti- Micropterus salmoides Rhabdovirus (MSRV) Activity In Vivo

Yingjie Jin; Fei Yang; Gengrong Zhang; Qing Yu; Gaoxue Wang; Fei Ling; Tianqiang Liu

doi:10.3390/v14071421

Synthesized Magnolol Derivatives Improve Anti- Micropterus salmoides Rhabdovirus (MSRV) Activity In Vivo

Viruses. 2022 Jun 28;14(7):1421. doi: 10.3390/v14071421.

Authors

Yingjie Jin¹, Fei Yang¹, Gengrong Zhang², Qing Yu³, Gaoxue Wang¹, Fei Ling¹, Tianqiang Liu^{1

2}

Affiliations

¹ College of Animal Science and Technology, Northwest A&F University, Xinong Road 22nd, Yangling 712100, China.
² Shenzhen Research Institute, Northwest A&F University, Gaoxin South 4th Road, Shenzhen Virtual University Park Building, High-Tech Industrial Park, Shenzhen 518057, China.
³ Guangxi Engineering Research Center for Fishery Major Diseases Control and Efficient Healthy Breeding Industrial Technology (GERCFT), Guangxi Key Laboratory of Aquatic Biotechnology and Modern Ecological Aquaculture, Guangxi Academy of Sciences, Nanning 530007, China.

Abstract

Micropterus salmoides rhabdovirus (MSRV) is a primary viral pathogen in largemouth bass aquaculture, which leads to tremendous economic losses yearly. Currently, there are no approved drugs for the treatment and control of this virus. Our previous studies screened the herb Magnolia officinalis from many traditional Chinese medicines, and we isolated and identified magnolol as its main active compound against multiple rhabdoviruses, including MSRV. On the basis of the structure-activity relationship and pharmacophore model of magnolol, two new magnolol derivatives, namely, hydrogenated magnolol and 2,2'-dimethoxy-magnolol, were designed and synthesized. Their anti-MSRV activities were systematically investigated both in vitro and in vivo. By comparing the half-maximal inhibitory concentration (IC₅₀), it was found that hydrogenated magnolol possessed a higher anti-MSRV activity than magnolol and 2,2'-dimethoxy-magnolol, with an IC₅₀ of 13.37 μM. Furthermore, hydrogenated magnolol exhibited a protective effect on the grass carp ovary (GCO) cell line by reducing the cytopathic effect induced by MSRV. Further studies revealed that hydrogenated magnolol did not directly impact virions or interfere with MSRV adsorption. It worked within the 6-8 h of the phase of virus replication. In vivo treatment of MSRV infection with magnolol and hydrogenated magnolol showed that they significantly improved the survival rate by 44.6% and 62.7%, respectively, compared to MSRV-infected groups. The viral load measured by the expression of viral glycoprotein in the organs including the liver, spleen, and kidney also significantly decreased when fish were intraperitoneally injected at a dose of 20 mg/kg. Altogether, the structural optimization of magnolol via hydrogenation of the propylene groups increased its anti-MSRV activity both in vitro and in vivo. These results may provide a valuable reference for anti-MSRV drug discovery and development in aquaculture.

Keywords: Micropterus salmoides rhabdovirus (MSRV); antiviral activity; largemouth bass; magnolol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bass*
Biphenyl Compounds / pharmacology
Female
Fish Diseases* / drug therapy
Lignans* / pharmacology
Lignans* / therapeutic use
Rhabdoviridae*

Substances

Biphenyl Compounds
Lignans
magnolol

Grants and funding

This research was funded by the National Natural Science Foundation of China (No. 31972841), the Chinese Universities Scientific Fund (No.2452020012), and the Guangdong Basic and Applied Basic Research Foundation (No.2020A1515111058).