Study: SARS-CoV-2 binds to yet another receptor type, C-lectin, in immune cells
New Pre-Print Study: SARS-CoV-2 Binds to Type-C Lectin Receptors In Immune Cells
Full Text PDF: https://www.biorxiv.org/content/10.1101/2020.08.09.242917v1.full.pdf
DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist
Michel Thepaut, Joanna Luczkowiak, Corinne Vives, Nuria Labiod, Isabelle Bally, Fatima Lasala, Yasmina Grimoire, Daphna Fenel, Sara Sattin, Nicole Thielens, Guy Schoehn, Anna Bernardi, Rafael Delgado, Franck Fieschi
The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis.
Competing Interest Statement:
The authors have declared no competing interest.
@cmartenson – Chris, do you think this new receptor binding is of any importance, and/or potentially indicative of an engineered nature for Sars-Cov-2?
Lectins are one of the biological systems apparently affected by 5G radiation: 5G may inhibit immune molecules called mannose-binding lectins (MBLs) which are primarily located on lung surfactant proteins which have been shown to express the “strongest anti-coronavirus activity” among lectins, targeting coronaviruses early in their replication cycle by preventing viral attachment to the ACE2 lung surface proteins. The lectin superfamily’s function “appears to be pattern recognition in the first line of defense in the pre-immune host. MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms” including viruses. So due to being one of the only anti-viral systems that can break down the signature glycoprotein shell that surrounds many viruses, including coronaviruses, MBL deficiency is conducive to repeat infections, particularly respiratory infections. Estimates suggest already 10-30% of the population is MBL deficient, before any 5G MBL inhibition.
So now it’s looking like SC2/hCoV-2019 can target C-type lectin receptor carbohydrate-binding domains? From a bioweapons/GoF perspective, it makes sense to target this one, along with CD4 and ACE2 (and the other known targets too?) — just as you would target MBLs if 5G was a military weapon.
Dr. Mayer, any comments?
Appreciate the post. This is just a minor update from what we already learned back in May
Back then I was reporting that DC-SIGN (CD209) and CLEC4M (CD299) were being docked via CD4 hijacking. This appears to be building on the known docking of CLRS.
These types of changes are expected with RNA viruses. They are adapting and finding new ways to infect various cells. Nothing malicious going on here. In August we saw new mutations in the hCoV-2019 RBD region
GH clade – N439K, S477N
GR clade – S477N
G clade – E484K
S477G mutation in various non-G clades
The GH mutations appear to have a more prominent impact for hACE2 docking. As we continue to monitor mutations within the virus we will discover more and more docking points.
Boss! Good info all the time!
Thank you guys for that information – the additional details were very helpful!