These are worthwhile points, George. This study underscores the difficulties and complexities of transitioning — all the way from an in vitro system to a cell-culture system using Lec2 living cells — to studies in the intact laboratory animal, and, thereafter, into carefully planned clinical studies. ☹
COMMENT: The authors’ approach would involve competitive inhibition — which works best when the concentration of the therapeutic exceeds the concentration of the target.
For a successful approach, the therapeutic also should be “in place,” before viral exposure, and on all surface areas where the virus might land. This would be very difficult in the alveolar region, because of its size (roughly the area of a tennis court). Also, mucociliary clearance will be functioning to remove this proposed drug in an aerosol.
In the past, most antivirals work through other mechanisms. Nonetheless, this study’s approach represents “a candle in darkness.” 😊
G, Chair, Department of Environmental and Public Health
University of Cincinnati College of Medicine
From: Nebert, Daniel
Sent: Thursday, June 23, 2022 4:34 PM
Due to the large outpouring of interest among GEITP’ers in looking-at/reading/examining the preprint described in the previous email — attached please find the Petitjean et al., pdf file (from the David Alsteens Lab) in Nat Commun, in press, accepted for publication on 22 May 2022 (not 10th of May, as erroneously written below). ☹ 😊😊
Subject: Researchers Discover a Possible Pathway to Prevent COVID Infection
This brief article just appeared on Medscape, summarizing in layman’s terms a paper from Belgium that was published on 10 May 2022 in Nature Communications. The article is written very conservatively, succinctly, no hysteria or hype, and very honestly about the researchers’ plans next to test this experimental system in mice, and then, if successful, they would move on into clinical studies. This experimental approach to prevent SARS-CoV-2 infections — seems to be a reasonable, and a plausible concept to tackle all SARS-CoV-2 variants (current and future) — irrespective of any and all viral mutations. Therefore, it is believed to be worth sharing this news ASAP. 😊
Researchers Find a Pathway to Prevent COVID Infection
Sabine Verschelde and Frédéric Soumois
25 May 2022
BRUSSELS — The Catholic University of Louvain (UCLouvain) in Belgium announced that its researchers have managed to identify the key that allows the COVID-19 virus to attack cells. What’s more, they have succeeded in closing the lock to block the virus and prevent it from interacting with the cell, thereby preventing infection.
UCLouvain emphasized that this discovery, which was published in the scientific journal Nature Communications on May 10, is sparking hope that an aerosol antiviral therapy can be developed that would eradicate the virus in the case of an infection or a high-risk contact.
For 2 years, the team under David Alsteens, PhD, a researcher at the UCLouvain Institute of Biomolecular Science and Technology, has been working hard to understand the precise molecular mechanisms the virus uses to infect a cell. They investigated the interaction between sialic acids (SAs), a type of sugar residue that is located on the surface of cells, and the SARS-CoV-2 spike (S) protein to clarify its role in the infection process.
It was already known that the function of the sugar residues that coat the cells is to promote cell recognition, thus enabling, in particular, viruses to identify their targets more easily, but also to provide them with a point of attachment and to facilitate infection of the cells.
The researchers have now discovered a variant of these sugars that interacts more strongly with the S protein than other sugars do.
In other words, the university explained, “they found the set of keys that allows the virus to open the cell door.” So, the researchers decided to catch the virus in its own trap, by preventing it from attaching to its host cell. To do this, they blocked the S protein’s points of attachment, thus suppressing any interaction with the cell surface, as if a padlock had been placed on the lock on the cell’s entry door.
Th researchers added that the advantage of this discovery is that it acts on the virus, irrespective of mutations.
The team of researchers will now conduct tests on mice to apply this blocking of virus binding sites and observe whether it works on the body. The results should make it possible to develop a clinical antiviral therapy administered by aerosol in the case of infection or severely at-risk contact.