Elucidation of cellular targets and exploitation of the receptor-binding domain of SARS-CoV-2 for vaccine and monoclonal antibody synthesis
Biological and Biomedical Sciences
The pandemic caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has resulted in over 452,822 deaths in the first twenty days of June 2020 due to the coronavirus virus disease 2019 (COVID-19). The SARS-CoV-2 uses the host angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the human cells where it replicates by using the cell protein synthesis mechanisms. The knowledge of the tissue distribution of ACE2 in human organs is therefore important to predict the clinical course of the COVID-19. Also important is the understanding of the viral receptor-binding domain (RBD) a region within the spike (S) proteins that enable the entry of the virus into the host cells to synthesize vaccine and monoclonal antibodies (mAbs). We performed an exhaustive search of human protein databases to establish the tissues that express ACE2 and performed an in-depth analysis like sequence alignments and homology modeling of the spike protein (S) of the SARS-CoV-2 to identify antigenic regions in the RBD that can be exploited to synthesize vaccine and mAbs. Our results show that ACE2 is widely expressed in human organs that may explain the pulmonary, systemic, and neurological deficits seen in COVID-19 patients. We show that though the S protein of the SARS-CoV-2 is a homolog of S protein of SARS-CoV-1, it has regions of dissimilarities in the RBD and transmembrane segments. We show peptide sequences in the RBD of SARS-CoV-2 that can bind to the MHC alleles and serve as effective epitopes for vaccine and mAbs synthesis.
Publication (Name of Journal)
Journal of Medical Virology
Baig, A. M.,
(2020). Elucidation of cellular targets and exploitation of the receptor-binding domain of SARS-CoV-2 for vaccine and monoclonal antibody synthesis. Journal of Medical Virology, 92(11), 2792-2803.
Available at: https://ecommons.aku.edu/pakistan_fhs_mc_bbs/852