Title

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

Authors

Garima Agarwal¹, Sanjay Gupta¹, Reema Gabrani^1, Amita Gupta², Vijay Kumar Chaudhary², Vandana Gupta^3*

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

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.