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. 2021 Jun 30;45(3):704-718.
doi: 10.3906/kim-2012-25. eCollection 2021.

Synthesis and molecular docking study of novel COVID-19 inhibitors

Zuhal Gerçek  1 , Deniz Ceyhan  2 , Erol Erçağ  2
Affiliations

Synthesis and molecular docking study of novel COVID-19 inhibitors

Zuhal Gerçek et al. Turk J Chem. .

Abstract

In 2020, the world tried to combat the corona virus (COVID-19) pandemic. A proven treatment method specific to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is still not found. In this study, seven new antiviral compounds were designed for COVID-19 treatment. The ability of these compounds to inhibit COVID-19's RNA processing was calculated by the molecular docking study. It has been observed that the compounds can have high binding affinities especially against NSP12 (between -9.06 and -8.00 kcal/mol). The molecular dynamics simulation of NSP12-ZG 7 complex proved the stability of interaction. The synthesis of two most active molecules was performed by one-pot reaction and characterized by FT-IR, 1H-NMR, 13C-NMR, and mass spectroscopy. The compounds presented with their synthesis are inhibitory core structures against SARS-CoV-2 infection.

Keywords: SARS-CoV-2; antiviral drug; molecular docking study; COVID-19.

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Conflict of interest statement

CONFLICT OF INTEREST: none declared

Figures

Figure 1
Figure 1
The skeleton of novel compounds.
Figure 2
Figure 2
General reaction route.,
Figure 3
Figure 3
Docking results of ZG-1 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-1 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-1 with NSP12 and NSP12-RNA complex, respectively.
Figure 4
Figure 4
Docking results of ZG-2 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-2 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-2 with NSP12 and NSP12-RNA complex, respectively.
Figure 5
Figure 5
Docking results of ZG-3 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-3 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-3 with NSP12 and NSP12-RNA complex, respectively.
Figure 6
Figure 6
Docking results of ZG-4 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-4 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-4 with NSP12 and NSP12-RNA complex, respectively.
Figure 7
Figure 7
Docking results of ZG-5 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-5 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-5 with NSP12 and NSP12-RNA complex, respectively.
Figure 8
Figure 8
Docking results of ZG-6 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-6 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-6 with NSP12 and NSP12-RNA complex, respectively.
Figure 9
Figure 9
Docking results of ZG-7 with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of ZG-7 on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of ZG-7 with NSP12 and NSP12-RNA complex, respectively.
Figure 10
Figure 10
Docking results of hydroxychloroquine with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of hydroxychloroquine on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of hydroxychloroquine with NSP12 and NSP12-RNA complex, respectively.
Figure 11
Figure 11
Docking results of remdesivir with NSP12 and NSP12-RNA complex. Figures a1 and a2 show the localization of remdesivir on the NSP12 and NSP12-RNA complex presented with the lipophilicity surface area, respectively. b1, b2 show 3D interactions and c1, c2 show 2D interactions of remdesivir with NSP12 and NSP12-RNA complex, respectively.
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References

    1. Zhou P Yang X.L Wang X G A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature . 2020;579:270–273. - PMC - PubMed
    1. Muralidharan N Sakthivel R Velmurugan D Gromiha M M. Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 protease against COVID-19. Journal of Biomolecular Structure and Dynamics . 2021;39:2673–2678. - PubMed
    1. Falzarano D Munster V. J. SARS MERS: recent insights into emerging coronaviruses. Nature Reviews Microbiology . 2016;14:523–534. - PMC - PubMed
    1. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet . 2020. - PMC - PubMed
    1. Zumla A Chan J F Azhar Hui D S C Yuen K Y. Coronaviruses — drug discovery and therapeutic options. Nature Reviews Drug Discovery . 2016;15:327–347. - PMC - PubMed

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