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Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach.
Bioinformation. 2019; 15(6):439-447.B

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31312082

Citation

Agarwal, Garima, et al. "Virtual Screening of Inhibitors Against Envelope Glycoprotein of Chikungunya Virus: a Drug Repositioning Approach." Bioinformation, vol. 15, no. 6, 2019, pp. 439-447.
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):439-447.
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 G, et al. Virtual Screening of Inhibitors Against Envelope Glycoprotein of Chikungunya Virus: a Drug Repositioning Approach. Bioinformation. 2019;15(6):439-447. PubMed PMID: 31312082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach. AU - Agarwal,Garima, AU - Gupta,Sanjay, AU - Gabrani,Reema, AU - Gupta,Amita, AU - Chaudhary,Vijay Kumar, AU - Gupta,Vandana, Y1 - 2019/06/15/ PY - 2019/04/01/received PY - 2019/04/16/accepted PY - 2019/7/18/entrez PY - 2019/7/18/pubmed PY - 2019/7/18/medline KW - CHIKV envelop glycoproteins KW - Chikungunya Virus (CHIKV) KW - Drug repositioning KW - Structure-based virtual screening SP - 439 EP - 447 JF - Bioinformation JO - Bioinformation VL - 15 IS - 6 N2 - 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. SN - 0973-2063 UR - https://www.unboundmedicine.com/medline/citation/31312082/Virtual_screening_of_inhibitors_against_Envelope_glycoprotein_of_Chikungunya_Virus:_a_drug_repositioning_approach L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31312082/ DB - PRIME DP - Unbound Medicine ER -
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