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 CC50, EC50, 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 105.8 TCID50/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 immunerelated
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.
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