Background:
COVID-19 has become pandemic with higher morbidity and mortality rates after its start from
Wuhan city of China. The infection by RNA virus, also known as SARS-CoV-2 or 2019-nCoV, from beta class of corona
viruses has been found to be responsible for COVID-19. Structural analysis and evidences have been indicated that
interaction between a segment of receptor binding domain (RBD) from S protein of virus and human angiotensin-converting
enzyme 2 (hACE2) is essential for cellular entry of virus.
Objective:
The current review put the light on structural aspects for inhibition of RBD-hACE2 interaction mediated cellular
entry of SARS-CoV-2.
Methods:
The present study provides a critical review of recently published information on RBD-hACE2 interaction and
its inhibitors to control SARS-CoV-2 infection. The review highlighted the structural aspects of interaction between RBDhACE2 and involved amino acid residues.
Results:
Recently, several studies are being conducted for inhibition of the SARS-CoV-2 attachment and entry to the human
cellular system. One of the important targets for viral invasion is its binding with cell surface receptor, hACE2, through
RBD on S-protein. Mimicking of three residues on ACE2 (Lys31, Glu35 and Lys353 on B chain) provided hot target
directed strategy for inhibition of early attachment of virus to the cell. Early screening of peptidic or non-peptidic molecules
for inhibition of RBD-hACE2 interaction has been raised the hope for potential therapeutics against COVID-19. The higher
affinity of molecules toward RBD than ACE2 is important factor for selectivity and minimization of ACE2 related adverse
events on cardiovascular system, brain, kidney, and foetus development during pregnancy.
Conclusion:
Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for
control of SARS-CoV-2 infection. Recently, published reports pointed out Lys31, Glu35 and Lys353 on B chain of ACE2
as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells.
Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding
pattern and potencies (IC50 values) which will help for further improvement in the selectivity.
