In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 1 ( 2021-1-25), p. e0245975-
Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency of international concern. The spike glycoprotein (S protein) of SARS-CoV-2 is a key target of antiviral drugs. Focusing on the existing S protein structure, molecular docking was used in this study to calculate the binding energy and interaction sites between 14 antiviral molecules with different structures and the SARS-CoV-2 S protein, and the potential drug candidates targeting the SARS-CoV-2 S protein were analyzed. Tizoxanide, dolutegravir, bictegravir, and arbidol were found to have high binding energies, and they effectively bind key sites of the S1 and S2 subunits, inhibiting the virus by causing conformational changes in S1 and S2 during the fusion of the S protein with host cells. Based on the interactions among the drug molecules, the S protein and the amino acid environment around the binding sites, rational structure-based optimization was performed using the molecular connection method and bioisosterism strategy to obtain Ti-2, BD-2, and Ar-3, which have much stronger binding ability to the S protein than the original molecules. This study provides valuable clues for identifying S protein inhibitor binding sites and the mechanism of the anti-SARS-CoV-2 effect as well as useful inspiration and help for the discovery and optimization of small molecule S protein inhibitors.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0245975
DOI:
10.1371/journal.pone.0245975.g001
DOI:
10.1371/journal.pone.0245975.g002
DOI:
10.1371/journal.pone.0245975.g003
DOI:
10.1371/journal.pone.0245975.g004
DOI:
10.1371/journal.pone.0245975.g005
DOI:
10.1371/journal.pone.0245975.g006
DOI:
10.1371/journal.pone.0245975.g007
DOI:
10.1371/journal.pone.0245975.g008
DOI:
10.1371/journal.pone.0245975.g009
DOI:
10.1371/journal.pone.0245975.g010
DOI:
10.1371/journal.pone.0245975.g011
DOI:
10.1371/journal.pone.0245975.g012
DOI:
10.1371/journal.pone.0245975.g013
DOI:
10.1371/journal.pone.0245975.t001
DOI:
10.1371/journal.pone.0245975.s001
DOI:
10.1371/journal.pone.0245975.s002
DOI:
10.1371/journal.pone.0245975.s003
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
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