Abstract
The green tea catechin epigallocatechin gallate (EGCG) exhibits antiviral activity against various viruses. Whether EGCG also inhibits the infectivity of circovirus remains unclear. In this study, we demonstrated the antiviral effect of EGCG on porcine circovirus type 2 (PCV2). EGCG targets PCV2 virions directly and blocks the attachment of virions to host cells. The microscale thermophoresis assay showed EGCG could interact with PCV2 capsid protein in vitro with considerable affinity (Kd = 98.03 ± 4.76 μM), thereby interfering with the binding of the capsid to the cell surface receptor heparan sulfate. The molecular docking analysis of capsid–EGCG interaction identified the key amino acids which formed the binding pocket accommodating EGCG. Amino acids ARG51, ASP70, ARG73 and ASP78 of capsid were found to be critical for maintaining the binding, and the arginine residues were also essential for the electrostatic interaction with heparan sulfate. The rescued mutant viruses also confirm the importance of the key amino acids of the capsid to the antiviral effect of EGCG. Our findings suggest that catechins could act as anti-infective agents against circovirus invasion, as well as provide the basic information for the development and synthesis of structure-based anti-circovirus drugs.
Highlights
Circovirus is one of the smallest non-enveloped viruses with a single-stranded circular genomicDNA and classified in the genus Circovirus of family Circoviridae [1]
The results showed that epigallocatechin gallate (EGCG) at a concentration of 100 μM did not generate significant cytotoxicity to PK-15 cells with a duration time of 24 h, 72 h, and 120 h, and EGCG at a concentration of 200 μM could produce cytotoxicity to cells, which limited the maximum concentration of EGCG at 100 μM (Figure 1b)
The infectivity of Porcine circovirus type 2 (PCV2) was significantly inhibited at the 100 μM EGCG treatment during the whole infective process, the virus titer of PCV2 infected cells with EGCG treatment showed a significant decrease at various time points compared to that without EGCG treatment (Figure 1c)
Summary
Circovirus is one of the smallest non-enveloped viruses with a single-stranded circular genomic. DNA and classified in the genus Circovirus of family Circoviridae [1]. It infects various species ranging from plants to animals with different pathogenicities [2]. Porcine circovirus type 2 (PCV2) is a prototype circovirus that causes significant morbidity and mortality in swine [3,4,5], and is associated with different syndromes, such as the post-weaning multisystemic wasting syndrome [6,7] and reproductive disorder [8]. The genome of PCV2 contains two major open reading frames (ORFs). ORF1 encodes the replicase protein (Rep) involved in rolling-circle viral DNA replication, while ORF2 encodes the unique viral structural protein capsid [9], which is involved in diverse and essential biological events during virus infection, such as virion attachment [10].
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