Antiviral effects of human placenta hydrolysate (Laennec®) against SARS-CoV-2 in vitro and in the ferret model

J Microbiol. 2021 Nov;59(11):1056-1062. doi: 10.1007/s12275-021-1367-2. Epub 2021 Oct 6.

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 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 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.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / pharmacology
  • Adenosine Monophosphate / therapeutic use
  • Alanine / analogs & derivatives*
  • Alanine / pharmacology
  • Alanine / therapeutic use
  • Animals
  • Antiviral Agents / therapeutic use*
  • COVID-19 Drug Treatment*
  • Chlorocebus aethiops
  • Female
  • Ferrets
  • Humans
  • Male
  • Placenta / chemistry*
  • Pregnancy
  • Protein Hydrolysates* / pharmacology
  • Protein Hydrolysates* / therapeutic use
  • SARS-CoV-2 / drug effects*
  • Vero Cells
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Protein Hydrolysates
  • remdesivir
  • Adenosine Monophosphate
  • Alanine