How we are helping the field of Medical Research
Squeaky Clean Jan, is excited to announce our participation in the fight against COVID-19.
How is this even possible? Well, thanks to technology and some amazing developers, they have come up with a way to join researchers throughout the world through [email protected]
What is folding?
2019-nCoV is a close cousin to SARS coronavirus (SARS-CoV),
and acts in a similar way. For both coronaviruses, the first step of
infection occurs in the lungs, when a protein on the surface of the
virus binds to a receptor protein on a lung cell. This viral protein is
called the spike protein, depicted in red in the image below, and the receptor is known as ACE2.
A therapeutic antibody is a type of protein that can block the viral
protein from binding to its receptor, therefore preventing the virus
from infecting the lung cell. A therapeutic antibody has already been
developed for SARS-CoV, but to develop therapeutic antibodies or small
molecules for 2019-nCoV, scientists need to better understand the
structure of the viral spike protein and how it binds to the human ACE2
receptor required for viral entry into human cells.
are not stagnant—they wiggle and fold and unfold to take on numerous
shapes. We need to study not only one shape of the viral spike protein,
but all the ways the protein wiggles and folds into alternative shapes
in order to best understand how it interacts with the ACE2 receptor, so
that an antibody can be designed. Low-resolution structures of the
SARS-CoV spike protein exist and we know the mutations that differ
between SARS-CoV and 2019-nCoV. Given this information, we are uniquely
positioned to help model the structure of the 2019-nCoV spike protein
and identify sites that can be targeted by a therapeutic antibody. We
can build computational models that accomplish this goal, but it takes a
lot of computing power.
This is where Squeaky Clean Jan comes in! With our computers working towards the same goal, we aim to help develop a therapeutic remedy as quickly as possible.
By using [email protected] here [LINK] . One protein from 2019-nCoV, a protease encoded by the viral RNA, has already been crystallized. Although the 2019-nCoV spike protein of interest has not yet been resolved bound to ACE2, our objective is to use the homologous structure of the SARS-CoV spike protein to identify therapeutic antibody targets.
Just a couple of projects we have helped with.
Structures of the closely related SARS-CoV spike protein bound by therapeutic antibodies may help rapidly design better therapies. The three monomers of the SARS-CoV spike protein are shown in different shades of red; the antibody is depicted in green. [PDB: 6NB7 https://www.rcsb.org/structure/6nb7]
(post authored by Ariana Brenner Clerkin)
6lu7 structure summary ‹ Protein Data Bank in Europe (PDBe) ‹ EMBL-EBI
https://www.ebi.ac.uk/pdbe/entry/pdb/6lu7 (accessed Feb 5, 2020).
Tian, X.; Li, C.; Huang, A.; Xia, S.; Lu, S.; Shi, Z.; Lu, L.; Jiang, S.; Yang, Z.; Wu, Y.; et al. Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody; preprint; Microbiology, 2020. https://doi.org/10.1101/2020.01.28.923011.
A. C.; Xiong, X.; Park, Y. J.; Tortorici, M. A.; Snijder, J.; Quispe,
J.; Cameroni, E.; Gopal, R.; Dai, M.; Lanzavecchia, A.; et al.
Unexpected Receptor Functional Mimicry Elucidates Activation of
Coronavirus Fusion. Cell 2019, 176, 1026-1039.e15. https://doi.org/10.2210/pdb6nb7/pdb.