Abstract:
The high rise pandemic of Coronavirus Disease 2019 (COVID-19) makes the world
face medical challenges associated with multifaceted nature of its pathology. SARSCoV-2 affects several organs and systems as it enters the host’s body one of which
is the brain. Over 80 million humans around the globe, including those with
neurodegenerative disease (NDD), have been diagnosed with coronavirus disease
2019 (COVID-19) to date. COVID-19 affects the brain in many ways including
direct infection of neural cells with SARS-CoV-2, severe systemic inflammation that
floods the brain with pro-inflammatory agents leading to damaging cells and leading
to symptoms presenting cognitive impairment. COVID-19 positive patients
showcase neurological symptoms leading to the belief that coronavirus disease plays
a role in neurodegenerative diseases. The most common NDD, Alzheimer’s disease
(AD) is characterized by its multifactorial nature leading to research on risk factors
that emphasizes on the inflammation of toxicity and mutual death of cells due to
amyloid beta and its conformers, namely monomeric and oligomeric forms.
Amyloid beta oligomers initiate toxicity and neural death of cells in AD. The main
aim of this study is to decipher the interactive association between toxic forms of
amyloid beta oligomer against COVID-19 main protease. We used PDB and
Pubchem for library retrieval that was loaded in to discovery studio to extract the
active binding site of main protease of SARS-CoV-2 and prepare ligands for
docking. Furthermore, we utilized PyRx for docking to investigating binding
energies of conformations attained, the best affinity ligands were formed into a
complex by the use of Pymol that were than visualized using Discovery studio where
2D interactions were also observed that later were further analyzed using Ligplot+
to get an insight on bond length and strength along with bond types. Aβ oligomer
31-35 binds actively to the active site of M-pro of SARS-CoV-2 at a high affinity
rate of -6.3kcal/mol. 6LU7 complex with amyloid 31-35 (Complex 1) when dockedXII
with the receptor of apoptotic pathway showed enhanced predictive association.
Bioinformatics tools in this research substantiated the important interactive partners
amongst amyloid oligomers to COVID-19 highlighting that SARS-Cov-2 may play
a role in apoptotic demise of cells ultimately leading to neurodegeneration.
