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. 2020 Jun;594(12):1960-1973.
doi: 10.1002/1873-3468.13806. Epub 2020 May 25.

Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs

Atsushi Hijikata  1 , Clara Shionyu-Mitsuyama  1 , Setsu Nakae  1 , Masafumi Shionyu  1 , Motonori Ota  2 , Shigehiko Kanaya  3 , Tsuyoshi Shirai  1
Affiliations

Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs

Atsushi Hijikata et al. FEBS Lett. 2020 Jun.

Abstract

The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 a pandemic. There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19.

Keywords: COVID-19; SARS-CoV; coronavirus; crude drug; drug repurposing; homology modeling.

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Figures

Fig. 1
Fig. 1
3C‐like proteinase–carfilzomib model. (A) Formula of (5s, 8s, 14r)‐ethyl 11‐(3‐amino‐3‐oxopropyl)‐8‐benzyl‐14‐hydroxy‐5‐isobutyl‐3, 6, 9, 12‐tetraoxo‐1‐phenyl‐2‐oxa‐4, 7, 10, 11‐tetraazapentadecan‐15‐oate (template ligand with ligand code AZP), carfilzomib, and lopinavir/ritonavir. (B) Overall structure of the model. (C) Close view of the carfilzomib binding site. Hydrogen bonds are shown in yellow lines.
Fig. 2
Fig. 2
Surface glycoprotein–ACE2–lisinopril/enalaprilat/captopril model. (A) Formula of lisinopril (ligand code LPR), enalaprilat (EAL), and captopril (X8Z). (B) Overall structure of the model. (C) Close view of the lisinopril/enalaprilat/captopril binding site. Hydrogen bonds are shown in yellow lines. Lisinopril, enalaprilat, and captopril were superposed, and the carbon atoms were colored light blue, gray, and magenta, respectively.
Fig. 3
Fig. 3
2′‐O‐Ribose methyltransferase (nsp16)–nsp10–sinefungin/tecadenoson/ selodenoson/trabodenoson model. (A) Formula of sinefungin (ligand code SFG), tecadenoson, selodenoson, and trabodenoson. (B) Overall structure of the model. (C) Close view of the binding site for sinefungin (SFG) and trabodenoson. Hydrogen bonds are shown in yellow lines.
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