PMID- 35729191
OWN - NLM
STAT- MEDLINE
DCOM- 20220623
LR  - 20221114
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jun 21
TI  - Studies on the antiviral activity of chebulinic acid against dengue and 
      chikungunya viruses and in silico investigation of its mechanism of inhibition.
PG  - 10397
LID - 10.1038/s41598-022-13923-6 [doi]
LID - 10397
AB  - Chebulinic acid (CA), originally isolated from the flower extract of the plant 
      Terminalia chebula, has been shown to inhibit infection of herpes simplex virus-2 
      (HSV-2), suggestively by inhibiting the host entry step of viral infection. Like 
      HSV-2, the dengue virus (DENV) and chikungunya virus (CHIKV) also use receptor 
      glycosaminoglycans (GAG) to gain host entry, therefore, the activity of CA was 
      tested against these viruses. Co-treatment of 8 microM CA with DENV-2 caused 2 log 
      decrease in the virus titer (4.0 log(10)FFU/mL) at 120 h post infection, compared 
      to virus control (5.95 log(10)FFU/mL). In contrast, no inhibitory effect of CA 
      was observed against CHIKV infection under any condition. The mechanism of action 
      of CA was investigated in silico by employing DENV-2 and CHIKV envelope 
      glycoproteins. During docking, CA demonstrated equivalent binding at multiple 
      sites on DENV-2 envelope protein, including GAG binding site, which have 
      previously been reported to play a crucial role in host attachment and fusion, 
      indicating blocking of these sites. However, CA did not show binding to the GAG 
      binding site on envelope protein-2 of CHIKV. The in vitro and in silico findings 
      suggest that CA possesses the ability to inhibit DENV-2 infection at the entry 
      stage of its infection cycle and may be developed as a potential therapeutic 
      agent against it.
CI  - (c) 2022. The Author(s).
FAU - Thomas, Naiju
AU  - Thomas N
AD  - Department of Biotechnology, School of Life Sciences, Central University of 
      Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, 305817, India.
FAU - Patil, Poonam
AU  - Patil P
AD  - Dengue and Chikungunya Group, ICMR-National Institute of Virology, 20-A Dr. 
      Ambedkar Road, Pune, Maharashtra, 411001, India.
FAU - Sharma, Anjana
AU  - Sharma A
AD  - Department of Biotechnology, School of Life Sciences, Central University of 
      Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, 305817, India.
FAU - Kumar, Sandeep
AU  - Kumar S
AD  - Department of Biotechnology, School of Life Sciences, Central University of 
      Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, 305817, India.
FAU - Singh, Vikas Kumar
AU  - Singh VK
AD  - Department of Biotechnology, School of Life Sciences, Central University of 
      Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, 305817, India.
FAU - Alagarasu, Kalichamy
AU  - Alagarasu K
AD  - Dengue and Chikungunya Group, ICMR-National Institute of Virology, 20-A Dr. 
      Ambedkar Road, Pune, Maharashtra, 411001, India.
FAU - Parashar, Deepti
AU  - Parashar D
AD  - Dengue and Chikungunya Group, ICMR-National Institute of Virology, 20-A Dr. 
      Ambedkar Road, Pune, Maharashtra, 411001, India.
FAU - Tapryal, Suman
AU  - Tapryal S
AD  - Department of Biotechnology, School of Life Sciences, Central University of 
      Rajasthan, NH-8, Bandarsindri, Ajmer, Rajasthan, 305817, India. 
      suman_tapryal@curaj.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220621
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antiviral Agents)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Hydrolyzable Tannins)
RN  - 18942-26-2 (chebulinic acid)
SB  - IM
MH  - Antiviral Agents/pharmacology/therapeutic use
MH  - *Chikungunya Fever/drug therapy
MH  - *Chikungunya virus/physiology
MH  - *Dengue/drug therapy
MH  - Glycosaminoglycans/metabolism
MH  - Herpesvirus 2, Human/metabolism
MH  - Humans
MH  - Hydrolyzable Tannins
PMC - PMC9213501
COIS- The authors declare no competing interests.
EDAT- 2022/06/22 06:00
MHDA- 2022/06/24 06:00
PMCR- 2022/06/21
CRDT- 2022/06/21 23:18
PHST- 2021/10/19 00:00 [received]
PHST- 2022/05/30 00:00 [accepted]
PHST- 2022/06/21 23:18 [entrez]
PHST- 2022/06/22 06:00 [pubmed]
PHST- 2022/06/24 06:00 [medline]
PHST- 2022/06/21 00:00 [pmc-release]
AID - 10.1038/s41598-022-13923-6 [pii]
AID - 13923 [pii]
AID - 10.1038/s41598-022-13923-6 [doi]
PST - epublish
SO  - Sci Rep. 2022 Jun 21;12(1):10397. doi: 10.1038/s41598-022-13923-6.