Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2 - PubMed (original) (raw)

Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2

Anamika Basu et al. Sci Rep. 2020.

Abstract

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Figure 1

Different activities of ACE2 protein and inhibitory role of spike protein.

Figure 2

Figure 2

Topology of membrane protein ACE2 (a) from PDBTM (PDB ID 6M18) and (b) from MemBrain 3.1.

Figure 3

Figure 3

Functions of allosteric protein.

Figure 4

Figure 4

Structures of phytochemicals.

Figure 5

Figure 5

(a) 3D structure for spike protein fragment Rmachandran plot, (b) from MolProbity server, (c) PROCHECK server.

Figure 6

Figure 6

SARS CoV2 S protein binding with human ACE2 receptor protein (generated by using UCSF Chimera software).

Figure 7

Figure 7

Distorted amino acids after spike protein binding in ACE2 receptor (generated by using UCSF Chimera software).

Figure 8

Figure 8

Spike protein binding with ACE2 in presence of hesperidin (generated by using UCSF Chimera software).

Figure 9

Figure 9

Spike protein binding with ACE2 in presence of emodin (generated by using UCSF Chimera software).

Figure 10

Figure 10

Spike protein binding with ACE2 in presence of anthraquinone (generated by using UCSF Chimera software).

Figure 11

Figure 11

Rhein binding with bound spike protein fragment and ACE2 (generated by using UCSF Chimera software).

Figure 12

Figure 12

Chrysin binding with bound spike protein fragment and ACE2 (generated by using UCSF Chimera software).

Figure 13

Figure 13

Chrysin binding cleft (generated by using UCSF Chimera software).

Figure 14

Figure 14

Docking structure of ACE2 bound with spike protein fragment in presence of (a) chloroquine (b) hydroxychloroquine (generated by using UCSF Chimera software).

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