249
Views
12
CrossRef citations to date
0
Altmetric
Research Articles

Targeting a conserved pocket (n-octyl-β-D–glucoside) on the dengue virus envelope protein by small bioactive molecule inhibitors

, , , ORCID Icon, , & show all
Pages 4866-4878 | Received 14 Aug 2020, Accepted 07 Dec 2020, Published online: 21 Dec 2020
 

Abstract

Dengue virus enters the cell by receptor-mediated endocytosis followed by a viral envelope (DENVE) protein-mediated membrane fusion. A small detergent molecule n-octyl-β-D–glucoside (βOG) occupies the hydrophobic pocket which is located in the hinge region plays a major role in the rearrangement. It has been reported that mutations occurred in this binding pocket lead to the alterations of pH threshold for fusion. In addition to this event, the protonation of histidine residues present in the hydrophobic pocket would also impart the conformational change of the E protein evidence this pocket as a promising target. The present study identified novel cinnamic acid analogs as significant blockers of the hydrophobic pocket through molecular modeling studies against DENVE. A library of seventy-two analogs of cinnamic acid was undertaken for the discovery process of DENV inhibitors. A Molecular docking study was used to analyze the binding mechanism between these compounds and DENV followed by ADMET prediction. Binding energies were predicted by the MMGBSA study. The Molecular dynamic simulation was utilized to confirm the stability of potential compound binding. The compounds CA and SCA derivatives have been tested against HSV-1 & 2 viruses. From the computational results, the compounds CA1, CA2, SCA 60, SCA 57, SCA 37, SCA 58, and SCA 14 exhibited favorable interaction energy. The compounds have in-vitro antiviral activity; the results clearly indicate that the compounds showed the activity against both the viruses (HSV-1 & HSV-2). Our study provides valuable information on the discovery of small molecules DENVE inhibitors.

Communicated by Ramaswamy H. Sarma

Disclosure statement

All the authors declare that there is no disclosure statement in this work.

Additional information

Funding

The work was supported by a research fellowship from JSS Academy of Higher Education & Research, Mysuru. (Order No.REG/DIR®/JSSURF/29(1)/2010-11 dated 23.05.2019).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,074.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.