Devyani Goswami, Amity University Kolkata
The spike proteins of the SARS-CoV-2 have been always the subject of interest in how it attaches to the human cells and causes the disease. Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for SARS-CoV (the virus observed in 2003); they are present in the epithelia of the lungs and small intestine.
The major difference between SARS-CoV-2 and SARS-CoV is the presence of a polybasic furin-type cleavage site, RRAR^S, at the S1/S2 junction of the former spike protein (S) which is absent in the later. Proteolytic cleavage of RRAR^S by furin exposes a conserved C-terminal motif RXXROH (R – arginine/lysine, X – any amino acid) in the S protein. These C-terminal sequences (CendR) binds and activates neuropilin (NRP1 and NRP2) receptors in cells.
The research was conducted on modified HEK-293T cells. ACE2 when expressed alone caused the infection to cells, while NRP-1 hardly caused any harm. Though, “co-expression with ACE2 and TMPRSS2 enhanced infection”. Monoclonal antibodies (mAbs) were designed to test the specificity of the NRP-1 dependent virus entry, which “blocked the extracellular b1b2 domain of NRP-1”. The mAbs failed to bind to the mutant b1b2 domain. Concludingly, TRP-1 is a host factor.
The sequence of SARS-CoV-2 spike proteins resembles a human protein that binds to NRP-1, by a small sequence of amino acid. Thus, the spike proteins of SARS-CoV-2 does indeed bind to NRP-1. “If you think of ACE2 as a door lock to enter cells, then NRP-1 could be the factor that directs the virus to the door. ACE2 is expressed at low levels in most cells. Thus, it is not easy for the virus to enter. Other factors like NRP-1 guide the virus to the door”. Although SARS-CoV-2 can enter into the host cell independently of the ACE2 when loads of the virus are high.
The authors concluded that it is too early to decide whether blocking NRP-1 directly could be a therapeutic approach, as this could lead to side effects. Further studies are solicited for this approach.
Also read: Fetus in Fetu analysis by modern Multimode Ultrasound
REFERENCE: 1) Neuropilin-1 is a host factor for SARS-CoV-2 infection
https://science.sciencemag.org/content/early/2020/10/19/science.abd3072
2) Neuropilin-1 Facilitates SARS-CoV-2 cell entry and infectivity
https://science.sciencemag.org/content/early/2020/10/19/science.abd2985
3) SARS-CoV-2 uses a second receptor, Neuropilin-1, to infect human cells https://www.genengnews.com/news/sars-cov-2-uses-a-second-receptor-neuropilin-1-to-infect-human-cells/
Molecular Archaeology-Let’s rewrite the History with ancient DNA
Sayanti Pal, Amity University Kolkata Until the 1980s most of the researchers used to believe that no detectable genetic material is preserved in archaeological remains due to the rapid decay of bio-organic molecules. The invention of different molecular techniques made possible the detection and characterization of organic compounds present in archaeological remains. Reading the DNA sequence of […]