PMID- 31803807
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231019
IS  - 2347-3584 (Print)
IS  - 2347-3517 (Electronic)
IS  - 2347-3584 (Linking)
VI  - 30
IP  - 3
DP  - 2019 Sep
TI  - In silico study of chikungunya polymerase, a potential target for inhibitors.
PG  - 394-402
LID - 10.1007/s13337-019-00547-0 [doi]
AB  - Non-structural protein 4 (nsP4) polymerase of chikungunya virus (CHIKV) has a 
      crucial role in genome replication and hence could act as a promising target for 
      novel therapeutics. Though, nsP4 is important in viral life cycle, but it is less 
      explored as therapeutic target. The catalytic core of nsP4 Polymerase includes 
      conserved GDD motif which is present not only across different CHIKV strains but 
      also across other Alphaviruses. This emphasizes the uniqueness and importance of 
      this motif in the functioning of nsP4 polymerase and hence, we focused on GDD 
      motif for docking of drug molecules. Herein, a model of nsP4 polymerase was 
      developed using Swiss Model, validated by Ramachandran plot and molecular dynamic 
      simulation. Molecular docking was performed using LeadIT FlexX flexible docking 
      module with FDA approved drug molecule library. On the basis of flexX score, top 
      5 leads with flexX scores - 33.7588, - 30.2555, - 29.6043, - 28.916 and - 28.5042 
      were selected. The bonding pattern of these leads were analysed in discovery 
      studio and were further screened on the basis of molecular dynamic simulation 
      studies. Simulation analysis revealed that only the top lead, Mitoxantrone 
      Hydrochloride which is an anticancer drug and is currently indicated in leukemias 
      and lymphomas interacted favourably and stably with nsP4. Our findings suggest 
      that Mitoxantrone Hydrochloride can be a potential novel inhibitor of CHIKV 
      polymerase and should be further validated by in vitro assays.
CI  - (c) Indian Virological Society 2019.
FAU - Ghildiyal, Ritu
AU  - Ghildiyal R
AUID- ORCID: 0000-0002-5504-0857
AD  - 1Department of Biotechnology, Center for Emerging Diseases, Jaypee Institute of 
      Information Technology, Noida, UP 201309 India. GRID: grid.419639.0. ISNI: 0000 
      0004 1772 7740
FAU - Gupta, Sanjay
AU  - Gupta S
AD  - 1Department of Biotechnology, Center for Emerging Diseases, Jaypee Institute of 
      Information Technology, Noida, UP 201309 India. GRID: grid.419639.0. ISNI: 0000 
      0004 1772 7740
FAU - Gabrani, Reema
AU  - Gabrani R
AD  - 1Department of Biotechnology, Center for Emerging Diseases, Jaypee Institute of 
      Information Technology, Noida, UP 201309 India. GRID: grid.419639.0. ISNI: 0000 
      0004 1772 7740
FAU - Joshi, Gopal
AU  - Joshi G
AUID- ORCID: 0000-0002-6238-9926
AD  - 2Centre for Innovation in Infectious Disease Research, Education and Training, 
      University of Delhi South Campus, Benito Juarez Marg, New Delhi, 110021 India. 
      GRID: grid.8195.5. ISNI: 0000 0001 2109 4999
FAU - Gupta, Amita
AU  - Gupta A
AD  - 2Centre for Innovation in Infectious Disease Research, Education and Training, 
      University of Delhi South Campus, Benito Juarez Marg, New Delhi, 110021 India. 
      GRID: grid.8195.5. ISNI: 0000 0001 2109 4999
FAU - Chaudhary, V K
AU  - Chaudhary VK
AD  - 2Centre for Innovation in Infectious Disease Research, Education and Training, 
      University of Delhi South Campus, Benito Juarez Marg, New Delhi, 110021 India. 
      GRID: grid.8195.5. ISNI: 0000 0001 2109 4999
FAU - Gupta, Vandana
AU  - Gupta V
AD  - 3Department of Microbiology, Ram Lal Anand College, University of Delhi South 
      Campus (UDSC), Benito Juarez Marg, New Delhi, 110021 India. GRID: grid.8195.5. 
      ISNI: 0000 0001 2109 4999
LA  - eng
PT  - Journal Article
DEP - 20191026
PL  - India
TA  - Virusdisease
JT  - Virusdisease
JID - 101624144
PMC - PMC6864021
OTO - NOTNLM
OT  - Catalytic triad
OT  - Chikungunya virus (CHIKV)
OT  - Molecular docking
OT  - RNA dependent RNA polymerase
COIS- Conflict of interestThe authors declare that they have no conflict of interest.
EDAT- 2019/12/06 06:00
MHDA- 2019/12/06 06:01
PMCR- 2020/09/01
CRDT- 2019/12/06 06:00
PHST- 2019/03/17 00:00 [received]
PHST- 2019/07/15 00:00 [accepted]
PHST- 2019/12/06 06:00 [entrez]
PHST- 2019/12/06 06:00 [pubmed]
PHST- 2019/12/06 06:01 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - 547 [pii]
AID - 10.1007/s13337-019-00547-0 [doi]
PST - ppublish
SO  - Virusdisease. 2019 Sep;30(3):394-402. doi: 10.1007/s13337-019-00547-0. Epub 2019 
      Oct 26.