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

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-ß) 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.

Identification, protein antiglycation, antioxidant, antiproliferative, and molecular docking of novel bioactive peptides produced from hydrolysis of Lens culinaris.

Bioactive peptides produced from natural sources are considered as strategic target for drug discovery. Hyperglycemia caused protein glycation alters the structure of many tissues that impairs their functions and lead complications diseases in human body. This study investigated the bioactive peptides produced from red and brown Lens culinaris that might inhibit protein glycation to prevent diabetic complications. In this study, red and brown Lens culinaris protein hydrolysates were prepared by tryptic digestion, using an enzyme/substrate ratio of 1:20 (g/g), at 37°C, 12 hr then peptide fractions <3 kDa were filtered by using ultrafiltration membranes. Protective ability against protein glycation, DPPH radical scavenging, and anti-proliferative activities (on HepG2, MCF-7, and PC3 cell lines) of peptide fractions were assayed in vitro. Results showed that glycation was inhibited by peptides from 28.1% to 68.3% in different test model. PC3 cell line was more sensitive to the peptides which showed strong anticancer activity with lower IC50 (0.96 mg/ml). Peptide fractions were sequenced by HPLC-MS-MS. Twenty eight novel peptides sequences was identified. In silico study, two peptides could be developed as a potential bioactive peptides exhibited antiglycation, antioxidant, and antiproliferative activities. PRACTICAL APPLICATIONS: Peptides are becoming an emerging source of medications with the development of new technologies. We have selected Lens Culinaris as one of the rich sources of proteins to explore novel bioactive peptides encapsulated in its seeds. Peptides fractions demonstrated protective ability against protein glycation, strong antioxidant potential, and promising antiproliferative activity. We have identified 28 novel peptides and molecular docking study revealed that some peptides showed strong binding potential to insulin receptor and ACE. Thus, these peptides might be used to manage diabetes complication as well as COVID-19 disease due to their interaction with ACE. However, those peptides needs to be further studied as a potential new drug.