Abstract:
The spread of the COVID-19 infectious disease that is caused by the SARS-CoV-2 virus (severe
acute respiratory syndrome coronavirus 2) has been a huge threat to the people of Sri Lanka and
worldwide. It has stirred a global health crisis since 2019 which has led to the declaration of a a
public health emergency of international concern by the World Health Organisation. Owing to its
novelty, there is a lack of effective therapeutic options to combat the viral infection. To better
appreciate key secondary level interactions leading to the structural complexity, a computational
structural analysis of secondary and super secondary structures (motifs) of the SARS-CoV-2 S
protein (RCSB PDB ID: 5X5B) was carried out. The three-dimensional prefusion structure of the S
protein was first structurally characterized using the ProFunc server tool, followed by analysis of
molecular graphics of secondary and super secondary structures as well as torsion angles of helical
sequences using RasMol program and STRIDE visual assignment tool, respectively. Three
distinguished protein chains namely A, B and C were identified from the prefusion three-dimensional
structure of the SARS-CoV-2 spike glycoprotein. The protein chain A is represented with the
identical chains of B and C with 1033 protein residues. Among the 14 β sheets of the chain A, 9 are
observed to be formed from more than two strands. The present work identifies a special region of
irregular β sheet in the S protein of the prefusion conformation which is experimentally verified in
previous optical spectra studies of SARS-CoV-2 proteins. Helical turns show a large deviation from
an ideal helix by 9.8 Å. Interhelical interactions are observed to experience the highest negative
interaction angle of magnitude 162.800. The most occurring non-flexible β turns may or may not be
stabilized by hydrogen bonds. This study emphasizes the need for further investigation of fused
conformation of SARS-CoV-2 virus in the light of current urgency of establishing optimal treatment
strategies for COVID-19.
Keywords: SARS-CoV-2; Computational analysis; Prefusion conformation; Spike protein
