PMID- 35567429
OWN - NLM
STAT- MEDLINE
DCOM- 20221012
LR  - 20221207
IS  - 1097-0134 (Electronic)
IS  - 0887-3585 (Print)
IS  - 0887-3585 (Linking)
VI  - 90
IP  - 11
DP  - 2022 Nov
TI  - Molecular interactions and inhibition of the SARS-CoV-2 main protease by a 
      thiadiazolidinone derivative.
PG  - 1896-1907
LID - 10.1002/prot.26385 [doi]
AB  - We report molecular interactions and inhibition of the main protease (M(Pro) ) of 
      SARS-CoV-2, a key enzyme involved in the viral life cycle. By using a 
      thiadiazolidinone (TDZD) derivative as a chemical probe, we explore the 
      conformational dynamics of M(Pro) via docking protocols and molecular dynamics 
      simulations in all-atom detail. We reveal the local and global dynamics of M(Pro) 
      in the presence of this inhibitor and confirm the inhibition of the enzyme with 
      an IC(50) value of 1.39 +/- 0.22 muM, which is comparable to other known inhibitors 
      of this enzyme.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Andrzejczyk, Jacob
AU  - Andrzejczyk J
AD  - Department of Chemical Engineering, University of New Hampshire, Durham, New 
      Hampshire, USA.
FAU - Jovic, Katarina
AU  - Jovic K
AD  - Department of Molecular, Cellular, and Biomedical Services, University of New 
      Hampshire, Durham, New Hampshire, USA.
FAU - Brown, Logan M
AU  - Brown LM
AD  - Department of Molecular, Cellular, and Biomedical Services, University of New 
      Hampshire, Durham, New Hampshire, USA.
FAU - Pascetta, Valerie G
AU  - Pascetta VG
AD  - Department of Molecular, Cellular, and Biomedical Services, University of New 
      Hampshire, Durham, New Hampshire, USA.
FAU - Varga, Krisztina
AU  - Varga K
AD  - Department of Molecular, Cellular, and Biomedical Services, University of New 
      Hampshire, Durham, New Hampshire, USA.
FAU - Vashisth, Harish
AU  - Vashisth H
AUID- ORCID: 0000-0002-2087-2880
AD  - Department of Chemical Engineering, University of New Hampshire, Durham, New 
      Hampshire, USA.
LA  - eng
GR  - P20 GM113131/GM/NIGMS NIH HHS/United States
GR  - R35 GM138217/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20220603
PL  - United States
TA  - Proteins
JT  - Proteins
JID - 8700181
RN  - 0 (Antiviral Agents)
RN  - 0 (Azoles)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 3.4.22.- (3C-like proteinase, SARS-CoV-2)
RN  - EC 3.4.22.28 (Coronavirus 3C Proteases)
SB  - IM
MH  - Antiviral Agents/chemistry/pharmacology
MH  - Azoles/*chemistry
MH  - Coronavirus 3C Proteases
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Molecular Dynamics Simulation
MH  - Protease Inhibitors/chemistry/pharmacology
MH  - *SARS-CoV-2
MH  - Viral Nonstructural Proteins/chemistry
MH  - *COVID-19 Drug Treatment
PMC - PMC9347825
MID - NIHMS1808029
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - docking
OT  - main protease
OT  - molecular dynamics
OT  - thiadiazolidinone
COIS- The authors declare no conflicts of interest.
EDAT- 2022/05/15 06:00
MHDA- 2022/10/13 06:00
PMCR- 2022/06/03
CRDT- 2022/05/14 07:03
PHST- 2022/04/17 00:00 [revised]
PHST- 2021/10/16 00:00 [received]
PHST- 2022/05/10 00:00 [accepted]
PHST- 2022/05/15 06:00 [pubmed]
PHST- 2022/10/13 06:00 [medline]
PHST- 2022/05/14 07:03 [entrez]
PHST- 2022/06/03 00:00 [pmc-release]
AID - PROT26385 [pii]
AID - 10.1002/prot.26385 [doi]
PST - ppublish
SO  - Proteins. 2022 Nov;90(11):1896-1907. doi: 10.1002/prot.26385. Epub 2022 Jun 3.