Spike
glycoprotein found on the surface of SARS-CoV-2 (SARS-CoV-2S) is a class I
fusion protein which helps the virus in its initial attachment with human
Angiotensin converting enzyme 2 (ACE2) receptor and its consecutive fusion with
the host cells. The attachment is mediated by the S1 subunit of the protein via
its receptor binding domain. Upon binding with the receptor the protein changes
its conformation from a pre-fusion to a post-fusion form. The membrane fusion
and internalization of the virus is brought about by the S2 domain of the spike
protein. From ancient times people have relied on naturally occurring
substances like phytochemicals to fight against diseases and infection. Among these phytochemicals, flavonoids and
non-flavonoids have been found to be the active source of different
anti-microbial agents. Recently, studies
have shown that these phytochemicals have essential anti-viral activities. We
performed a molecular docking study using 10 potential naturally occurring
flavonoids/non-flavonoids against the SARS-CoV-2 spike protein and compared
their affinity with the FDA approved drug hydroxychloroquine (HCQ).
Interestingly, the docking analysis suggested that C-terminal of S1 domain and
S2 domain of the spike protein are important for binding with these compounds.
Kamferol, curcumin, pterostilbene, and
HCQ interact with the C-terminal of S1
domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively.
Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and
apigenin on the other hand, interact with the S2 domain of spike protein
with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2,
-7.9, -7.7 Kcal/mol, respectively. Our study suggested that, these
flavonoid and non-flavonoid moieties have significantly high binding affinity
for the two main important domains of the spike protein which is responsible
for the attachment and internalization of the virus in the host cell and their
binding affinities are much higher compared to that of HCQ. In addition, ADME (absorption, distribution, metabolism and
excretion) analysis also suggested that these compounds consist of drug likeness
property which may help for further explore as anti-SARS-CoV-2 agents. Further,
in vitro and in vivo study of these compounds will provide a clear path for the
development of novel compounds that would most likely prevent the receptor
binding or internalization of the SARS-CoV-2 spike protein and therefore could
be used as drugs for COVID-19 therapy.