Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk

Abstract

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is an extremely complex with nutritional composition to nourish infants and protect them from different kinds of infection diseases and also SARS-CoV-2 infection. Previous studies have found that breastmilk exhibited potent antiviral activity against SARS-CoV-2 infection. However, it is still unknown which component(s) in the breastmilk is responsible for its antiviral activity. Here, we identified Lactoferrin (LF), MUC1 and α-Lactalbumin (α-LA) from human breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in vitro confirmation that inhibited SARS-CoV-2 infection and analyzed their antiviral activity using the SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP) in the Huh7.5, Vero E6 and Caco-2-N cell lines. Additionally, we found that LF and MUC1 could inhibit viral attachment, entry and post-entry replication, while α-LA just inhibit viral attachment and entry. Importantly, LF, MUC1 and α-LA possess potent antiviral activities towards not only wild-type but also variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Moreover, LF from other species (e.g., bovine and goat) is still capable of blocking viral attachment to cellular heparan sulfate. Taken together, our study provided the first line of evidence that human breastmilk components (LF, MUC1 and α-LA) are promising therapeutic candidates warranting further development or treatingVID-19 given their exceedingly safety levels.

Preventative and therapeutic potential of animal milk components against COVID‐19: A comprehensive review

“…Whey proteins (LF, ALA, and mucin1) obtained from human breast milk showed strong antiviral roles against different SARS-CoV-2 variants (α, β, γ, and κ), as these can inhibit viral infection at all stages of replication cycle, that is, attachment [by binding to TA B L E 3 Antiviral roles of whey proteins (α-lactalbumin and β-lactoglobulin) against some important pathogenic viruses of humans. heparan sulfate proteoglycans (HSPG) receptors], entrance, and postentrance replication (Lai et al, 2021). Two peptides, that is, "Ala-Leu-Pro-Met-His-Ile-Arg" and "Ile-Pro-Ala-Val-Phe-Lys," isolated from BLG of goat milk, and were reported to block SARS-CoV-2 entrance into host cells by showing inhibitory effects on ACE2 and DPP-4 receptors, as analyzed on the basis of docking scores in an in silico study (Cakir et al, 2021).…”