Whey proteins are meeting the interest of many researchers for their numerous intrinsic biological properties, starting from the antimicrobial ones. In the last two years, then, there is a great ferment around lactoferrin, since in vitro studies have shown an important antiviral activity against Sars-CoV-2.
Recently, many experimental evidences on the antiviral activity, and in particular on the anti-Sars-CoV-2 activity, of these proteins have been accumulated.
Certainly lactoferrin has been the most studied protein in this aspect. However, we must not forget that also other whey proteins are involved in the so-called natural immunity or innate immunity, that is in the protection provided to the infant by the mother through milk. First of all, it is necessary to mention lysozyme which, besides having antibacterial activity, has been shown in vitro to have also antiviral activity. Also other whey proteins, such as, for example, β-lactoglobulin and lactoperoxidase, have shown in vitro antiviral activity and, in particular, anti Sars-CoV-2.
Generally, the main mechanism of action is traced back to an interference of the whey protein on the attachment of the virus to the target cells of the host. This interference can be more or less specific and directed towards the lipoprotein or glycoprotein structures of the virus and/or the host cell. In some cases it has been demonstrated a strong binding, even if not very specific, based mainly on an electrostatic interaction, while, in others, it has been shown a quite specific binding by certain structural domains present on the surface of whey proteins. In addition, two other mechanisms of action have been hypothesized for lactoferrin, which include both the stimulation of interferon production, which inhibits viral replication, and the inhibition of cathepsin-L, a protease essential for the release of Sars-CoV-2 from the endosome of the host cell.
There is no doubt that in vitro lactoferrin exerts an antiviral action against several viruses and also against Sars-CoV-2. However, clinical data are not yet conclusive because, on the one hand, it is difficult for intact lactoferrin to reach in vivo the entry sites of the virus in the host cell and, on the other hand, the clinical studies performed so far are generally open-label, retrospective and with few patients.
As for all drugs, in order to quantify exactly the degree of protection of lactoferrin from Covid-19, prospective, randomized, double-blind studies on many patients and possibly multicenter would be required. In other words, it would be necessary to administer lactoferrin or a placebo or another reference drug to many thousands of people, possibly in different hospital centers located in different countries and then compare the effectiveness of treatment with lactoferrin to the results obtained with placebo or reference drugs. However, it is easy to understand how such a clinical trial is ethically difficult to carry out in the presence of a disease that has a high index of danger such as Covid-19.
Milk proteins, and in particular lactoferrin, taken orally or carried by lipid carriers, have a great advantage: except for allergies, they are harmless and can provide a limited protection from “natural immunity” even in adults, particularly in the gastro-intestinal tract, which can be a gateway to the Sars-CoV-2 virus.

