The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

At 50 nmol/L of peruvoside treatment, EV-A71’s strain (representative of positive sense RNA viruses) viral titre showed 4-log₁₀ units of reduction and at 100nmol/L EV-A71 were undetected via plague assay. The same treatment were performed on four families of positive-sense RNA viruses: Picornaviridae, Coronaviridae, Togaviridae and Flaviviridae, one family of DNA virus, Herpesviridae and two family of single-stranded Negative-sense RNA virus, Orthomyxoviridae and Paramyxoviridae. It was demonstrated that peruvoside treatment reduced viral titres in a dosage-dependent manner for all tested viruses similar to picornaviruses.

In addition, in vivo efficacy of peruvoside was tested in BALB/C murine model of EV-A71 infection. The efficacy of peruvoside as therapeutics achieved 100% protective effect (P*=0.0043) of up to 21 days of post lethal infection (Fig. 1).

Figure 1. Peruvoside inhibits the replication of EV-A71. Bars represent the viral titre and lines represent relative cell viability.

Moreover, peruvoside-treated EV-A-71-infected mice retained tissue integrity and has no obvious necrosis in small intestine and hind limb skeletal muscles (Fig. 2).

Figure 2. (A) Survival curve of intraperitoneally injected 7-day-old BALB/c mice with 1 × 10⁵ PFU EV-A71 (HFM41) and 0.59 mg/kg peruvoside-treated mice (n = 6 mice per group) monitored up to 3-weeks post-infection displayed a significant correlation (^∗P = 0.0043) by log-rank (Mantel-Cox) test. 

Results also revealed Golgi stacks vesiculation within a perinuclear distribution pattern upon treatment with peruvoside in cells infected with EV-A71 (Fig. 3A), CHIKV (Fig. 3B), ZIKV (Fig. 3C), DENV2 (Fig. 3D) and MHV (Fig. 3E). Moreover, Golgi vesiculation was associated with the absence of viral dsRNA in cells infected with EV-A71 and CHIKV observed at 12  and 24 hpi, respectively.

Figure 3.  Peruvoside treatment induced Golgi vesiculation and reduced viral RNA replication

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^aYong Loo Lin School of Medicine, National University Health System, National University of Singapore. ^bFaculty of Veterinary Medicine, Khonkaen University, Thailand. ^cInfectious Disease Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. ^dInstitute of Molecular and Cell Biology, Agency of Science, Technology and Research (A*STAR), Singapore. ^eLee Kong Chian School of Medicine, Nanyang Technological University, Singapore. ^fNUSMed Biosafety Level 3 core facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.