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 drug 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 computational approach. The PDB structure of spike and RdRp and predicted structure of helicase proteins were docked with 100 approved antiviral drugs, natural compounds and some other
chemical compounds.
Results:
The anti-SARS ligands EK1 and CID_23631927, and NCGC00029283 are potential entry inhibitor as it showed affinity with immunogenic receptor binding domain (RBD) of 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 inhibitor as they showed affinity with RBD, Ploop containing nucleoside triphosphate hydrolase and 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 inhibitor.
Conclusion:
Several potential ligands were identified with already known anti-HCoVs activities. Furthermore, as our study
showed that some of the ligands acted as both entry or replication inhibitor against SARS-CoV-2, it is envisaged that a
combination of either inhibitors with a dual mode of action would prove to be a much desired therapeutic option against this
viral infection.
A novel hydrophobic diheme c -type cytochrome. Purification from Corynebacterium glutamicum and analysis of the QcrCBA operon encoding three subunit proteins of a putative cytochrome reductase complex 1The nucleotide sequences reported in this paper have been submitted to the DDBJ/GenBank/EMBL Data Bank with accession number AB038380. 1