PMID- 34008647
OWN - NLM
STAT- MEDLINE
DCOM- 20210615
LR  - 20220816
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 23
IP  - 22
DP  - 2021 Jun 9
TI  - Antiviral drug design based on the opening mechanism of spike glycoprotein in 
      SARS-CoV-2.
PG  - 12549-12558
LID - 10.1039/d1cp01045j [doi]
AB  - The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the 
      host cell after the receptor binding domain (RBD) of the virus spike (S) 
      glycoprotein binds to the human angiotensin-converting enzyme 2 (hACE2). This 
      binding requires the RBD to undergo a conformational change from a closed to an 
      open state. In the present study, a key pair of salt bridges formed by the side 
      chains of K537 and E619, residues at the interfaces of SD1 and SD2, respectively, 
      was identified to promote the opening of the RBD. Mutations of K537Q and E619D 
      reduced their side chain lengths and eliminated this pair of salt bridges; as a 
      result, the opening of the RBD was not observed in the MD simulations. Thus, 
      blocking the formation of this pair of salt bridges is a promising approach for 
      treating novel coronavirus disease 2019 (COVID-19). FDA approved drug molecules 
      were screened by their capabilities of blocking the formation of the key pair of 
      salt bridges, achieved by their positional stabilities in the cavity containing 
      the side chains of K537 and E619 formed in the interface between SD1 and SD2. 
      Simeprevir, imatinib, and naldemedine were identified to possess the desired 
      capability with the most favorable interaction energies.
FAU - Mao, Ruichao
AU  - Mao R
AUID- ORCID: 0000-0002-5494-7465
AD  - Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, 
      Huazhong Agricultural University, Wuhan, Hubei 430070, China. 
      gaojun@mail.hzau.edu.cn.
FAU - Bie, Lihua
AU  - Bie L
AUID- ORCID: 0000-0002-3334-493X
AD  - Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, 
      Huazhong Agricultural University, Wuhan, Hubei 430070, China. 
      gaojun@mail.hzau.edu.cn.
FAU - Xu, Maofeng
AU  - Xu M
AD  - Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, 
      Huazhong Agricultural University, Wuhan, Hubei 430070, China. 
      gaojun@mail.hzau.edu.cn.
FAU - Wang, Xiaocong
AU  - Wang X
AUID- ORCID: 0000-0002-5387-7389
AD  - Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, 
      Huazhong Agricultural University, Wuhan, Hubei 430070, China. 
      gaojun@mail.hzau.edu.cn.
FAU - Gao, Jun
AU  - Gao J
AUID- ORCID: 0000-0002-6692-1828
AD  - Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, 
      Huazhong Agricultural University, Wuhan, Hubei 430070, China. 
      gaojun@mail.hzau.edu.cn.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Antiviral Agents)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 03KSI6WLXH (naldemedine)
RN  - 5S6W795CQM (Naltrexone)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - 9WS5RD66HZ (Simeprevir)
SB  - IM
EIN - Phys Chem Chem Phys. 2021 May 28;:. PMID: 34046655
MH  - Antiviral Agents/chemistry/*pharmacology
MH  - *Drug Design
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Imatinib Mesylate/chemistry/pharmacology
MH  - Molecular Docking Simulation
MH  - Naltrexone/analogs & derivatives/chemistry/pharmacology
MH  - Protein Domains/drug effects
MH  - SARS-CoV-2/chemistry/*drug effects
MH  - Simeprevir/chemistry/pharmacology
MH  - Spike Glycoprotein, Coronavirus/*antagonists & inhibitors/chemistry/metabolism
EDAT- 2021/05/20 06:00
MHDA- 2021/06/16 06:00
CRDT- 2021/05/19 09:00
PHST- 2021/05/20 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2021/05/19 09:00 [entrez]
AID - 10.1039/d1cp01045j [doi]
PST - ppublish
SO  - Phys Chem Chem Phys. 2021 Jun 9;23(22):12549-12558. doi: 10.1039/d1cp01045j.