α-lactalbumin for COVID-19

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19), is spreading worldwide. Although the COVID-19 epidemic has passed its peak of transmission, the harm it has caused deserves our attention. Scientists are striving to develop medications that can effectively treat COVID-19 symptoms without causing any adverse reactions. SARS-CoV-2 inhibitory peptides derived from animal proteins have a wide range of functional activities in addition to safety. Identifying animal protein sources is crucial to obtaining SARS-CoV-2 inhibitory peptides from animal sources. This review aims to reveal the mechanisms of action of these peptides on SARS-CoV-2 and the possibility of animal proteins as a material source of SARS-CoV-2 inhibitory peptides. Also, it introduces the utilization of computer-aided design methods, phage display, and drug delivery strategies in the research on SARS-CoV-2 inhibitor peptides from animal proteins. In order to identify new antiviral peptides and boost their efficiency, we recommend investigating the interaction between SARS-CoV-2 inhibitory peptides from animal protein sources and non-structural proteins (Nsps) using a variety of technologies, including computer-aided drug approaches, phage display techniques, and drug delivery techniques. This article provides useful information for the development of novel anti-COVID-19 drugs.

AbstractThe 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.