Abstract
The COVID-19 pandemic has caused unprecedented health, social, and economic crises worldwide. However, to date, there is an only a limited effective treatment for this disease. Human placenta hydrolysate (hPH) has previously been shown to be safe and to improve the health condition in patients with hyperferritinemia and COVID-19. In this study, we aimed to determine the antiviral effects of hPH against SARS-CoV-2 in vitro and in vivo models and compared with Remdesivir, an FDA-approved drug for COVID-19 treatment. To assess whether hPH inhibited SARS-CoV-2 replication, we determined the CC 50 , EC 50 , and selective index (SI) in Vero cells by infection with a SARS-CoV-2 at an MOI of 0.01. Further, groups of ferrets infected with 10 5.8 TCID 50 /ml of SARS-CoV-2 and treated with hPH at 2, 4, 6 dpi, and compared their clinical manifestation and virus titers in respiratory tracts with PBS control-treated group. The mRNA expression of immune-related cytokines was determined by qRT-PCR. hPH treatment attenuated virus replication in a dose-dependent manner in vitro. In a ferret infection study, treatment with hPH resulted in minimal bodyweight loss and attenuated virus replication in the nasal wash, turbinates, and lungs of infected ferrets. In addition, qRT-PCR results revealed that the hPH treatment remarkably upregulated the gene expression of type I (IFN-α and IFN-β) and II (IFN-γ) IFNs in SARS-CoV-2 infected ferrets. Our data collectively suggest that hPH has antiviral efficacy against SARS-CoV-2 and might be a promising therapeutic agent for the treatment of SARS-CoV-2 infection.
Keywords: Laennec®; SARS-CoV-2; antiviral; ferret; interferon.
【저자키워드】 SARS-CoV-2, Antiviral, interferon, ferret, Laennec®, 【초록키워드】 COVID-19, Treatment, Cytokines, Gene Expression, Antiviral, Placenta, SARS-COV-2 infection, COVID-19 pandemic, qRT-PCR, Human, Infection, interferon, Remdesivir, lung, nasal, antiviral effects, cytokine, in vitro, Antiviral effect, COVID-19 treatment, Health, Lungs, therapeutic, Patient, antiviral efficacy, IFN, virus replication, therapeutic agent, respiratory tract, group, disease, SARS-CoV-2 replication, IFN-γ, Hyperferritinemia, Safe, IFN-α, virus titers, determined by, clinical manifestation, virus titer, Attenuated Virus, FDA-approved drug, IFN-β, dose-dependent manner, type I, Vero cells, ferrets, selective, TCID, mRNA expression, health condition, respiratory tracts, Vero Cell, effective, IMPROVE, MOI, shown, caused, addition, inhibited, treated, was determined, determine, PBS, upregulated, in vivo model, 【제목키워드】 Placenta, in vitro, Effect,