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Title

Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug
repositioning approach

 

Authors

Garima Agarwal1, Sanjay Gupta1, Reema Gabrani1, Amita Gupta2, Vijay Kumar Chaudhary2, Vandana Gupta3*

 

Affiliation

1Center for Emerging Diseases, Department of Biotechnology, Jaypee Institute of Information Technology, Noida, UP 201309, India: 2Centre for Innovation in Infectious Disease Research, Education and Training, University of Delhi South Campus, Benito Juarez Marg, New Delhi 110021, India: 3Department of Microbiology, Ram Lal Anand College, University of Delhi South Campus (UDSC), Benito Juarez Marg, New Delhi 110021, India.

 

Email

Vandana Gupta - E-mail: vandanagupta72@rediffmail.com; Phone: +91 7838004880

 

Article Type

Research Article

 

Date

Received April 1, 2019; Accepted April 16, 2019; Published June 15, 2019

 

Abstract

Chikungunya virus (CHIKV) a re-emerging mosquito-borne alpha virus causes significant distress which is further accentuated in the lack of specific therapeutics or a preventive vaccine, mandating accelerated research for anti-CHIKV therapeutics. In recent years, drug repositioning has gained recognition for the curative interventions for its cost and time efficacy. CHIKV envelope proteins are considered to be the promising targets for drug discovery because of their essential role in viral attachment and entry in the host cells. In the current study, we propose structure-based virtual screening of drug molecule on the crystal structure of mature Chikungunya envelope protein (PDB 3N41) using a library of FDA approved drug molecules. Several cephalosporin drugs docked successfully within two binding sites prepared at E1-E2 interface of CHIKV envelop protein complex with significantly low binding energies. Cefmenoxime, ceforanide, cefotetan, cefonicid sodium and cefpiramide were identified as top leads with a cumulative score of -67.67, -64.90, -63.78, -61.99, and - 61.77, forming electrostatic, hydrogen and hydrophobic bonds within both the binding sites. These shortlisted leads could be potential inhibitors of E1-E2 hetero dimer in CHIKV, hence might disrupt the integrity of envelope glycoprotein leading to loss of its ability to form mature viral particles and gain entry into the host.

 

Keywords

Chikungunya Virus (CHIKV); Drug repositioning; Structure-based virtual screening; CHIKV envelop glycoproteins.

 

Citation

Agarwal et al. Bioinformation 15(6): 439-447 (2019)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.