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Agarwal G, Gupta S, Gabrani R, et al. Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach. Bioinformation. 2019;15(6):439-447doi: 10.6026/97320630015439.
Agarwal, G., Gupta, S., Gabrani, R., Gupta, A., Chaudhary, V. K., & Gupta, V. (2019). Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach. Bioinformation, 15(6), 439-447. https://doi.org/10.6026/97320630015439
Agarwal, Garima, et al. "Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach." Bioinformation vol. 15,6 (2019): 439-447. doi: https://doi.org/10.6026/97320630015439
Agarwal G, Gupta S, Gabrani R, Gupta A, Chaudhary VK, Gupta V. Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach. Bioinformation. 2019 Jun 15;15(6):439-447. doi: 10.6026/97320630015439. eCollection 2019. PMID: 31312082; PMCID: PMC6614119.
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Bioinformation. 2019 Jun 15;15(6):439-447. doi: 10.6026/97320630015439. eCollection 2019.

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

Bioinformation

Garima Agarwal, Sanjay Gupta, Reema Gabrani, Amita Gupta, Vijay Kumar Chaudhary, Vandana Gupta

Affiliations

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

PMID: 31312082 PMCID: PMC6614119 DOI: 10.6026/97320630015439

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

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