Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected
around 13 million people and has caused more than 5.7 lakh deaths worldwide since December 2019. In
the absence of FDA approved drugs for its treatment, only symptomatic management is done.
Methods: We attempted to uncover potential therapeutic targets of spike, helicase, and RNA dependent
RNA polymerase (RdRp) proteins of the SARS-CoV-2 employing a computational approach. The PDB
structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved
anti-viral drugs, natural compounds, and some other chemical compounds.
Results: The anti-SARS ligands EK1 and CID 23631927, and NCGC00029283 are potential entry inhibitors
as they showed affinity with immunogenic Receptor Binding Domain (RBD) of the spike protein.
This RBD interacts with Angiotensin Converting Enzyme (ACE2) receptor, facilitating the entry of
virion in the host cells. The FDA approved drugs, including Nelfinavir, Saquinavir, Tipranavir, Setrobuvir,
Indinavir, and Atazanavir, showed potential inhibitory activity against targeted domains and thus,
may act as entry or replication inhibitor or both. Furthermore, several anti-HCoV natural compounds,
including Amentoflavone, Rutin, and Tannin, are also potential entry and replication inhibitors as they
showed affinity with RBD, P-loop containing nucleoside triphosphate hydrolase, and the catalytic domain
of the respective protein. Dithymoquinone showed significant inhibitory potential against the fusion
peptide of S2 domain. Importantly, Tannin, Dithymoquinone, and Rutin can be extracted from Nigella
sativa seeds and thus, may prove to be one of the most potential anti-SARS-CoV-2 inhibitors.
Conclusion: Several potential ligands were identified with already known anti-HCoVs activities. Furthermore,
as this study showed that some of the ligands acted as both entry and replication inhibitors
against SARS-CoV-2, it is envisaged that a combination of either inhibitor with a dual mode of action
would prove to be a much desired therapeutic option against this viral infection.