How do glycans get involved in SARS-CoV-2 infection?
The second wave of the new corona virus infection is hitting. The number of new infections in Tokyo yesterday reached 472. There are 195 people in Osaka, 181 in Aichi, 121 in Fukuoka, more than 100 in large cities. The speed of research on the new corona virus and the rapid increase in published papers are amazing. If the new corona virus (SRAS-CoV-2) infects humans, what are the receptors on cells that trigger the initiation of the infection? In response to the question, it is established that it must be ACE2 (Angiotensin Conversion Environment 2). For example, the following papers are helpful (but there are too many papers to be missed, please forgive me). https://science.sciencemag.org/content/367/6485/1444/tab-pdf https://science.sciencemag.org/content/367/6483/1260/tab-pdf However, in addition to ACE2, there is a report that ANPEP (Alanyl Minopepptidase) and DPP4 (Dipeptidyl Peptidase-4) can also be such receptors. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156119/pdf/main.pdf There is little exception that membrane proteins are heavily glycosylated. And both the S protein of the new corona virus and ACE2, which is the infected receptor, are strongly glycosylated. For example, in the following paper, it has been reported that various N-type glycans are expressed on S proteins, from Oligomannose to hybrid and Complex, and for O-type sugar chains, Core1 and Core2 type glycan structures are expressed. https://science.sciencemag.org/content/369/6501/330/tab-pdf On the other hand, for ACE2, an overview of the glycan modification is described in the following paper, and it can be seen that a very diverse glycans is expressed in the same way as the glycan modification of S protein. https://www.biorxiv.org/content/10.1101/2020.05.01.071688v1.full.pdf In this way, considering that a variety of glycans are expressed both on the S protein and the receptor side, there should always be an infection start with a sugar chain. In the following paper, it has been reported that S proteins strongly interact with DC-SIGN and MGL, which are C-type lectins, and also strongly interact with siglec-3, -9, and -10 sialic-3, -9, and -10, which are sialic acid binders. https://www.biorxiv.org/content/10.1101/2020.05.13.092478v1.full.pdf Taking this information into consideration together, the infection of the new corona virus is not ACE2 one side down, but peptidases (ANPEP, DPP4), but C-type lectin (DC-SIGN, MGL), and Siglec may also be involved. Moreover, these receptors are widely expressed in tissues in the body, including immune cells. What is even more interesting is the report that ABO blood type is related to the severity of the new coronavirus. https://www.nejm.org/doi/pdf/10.1056/NEJMoa2020283?articleTools=true From this paper, it can be found that people of type A are twice as severe as O-type humans. This suggests that anti-A antibodies may be suppressing sars-CoV-2 infections. Since anti-A antibodies are for the following type A antigen, it is considered that there is no doubt that this type of glycan structure is involved in infection in some way. Infectious diseases cannot be talked about without glycans, I think. Furthermore, it is so mysterious that there must be an unknown Factor-X to explain everything reasonably; why mortality rates in Asia and Oceania are so low comparing with those of Europe and […]Read more