In silico studies of the inhibition mechanism of dengue with papain

Abstract

Dengue virus is becoming a major global disease; the envelope protein is the major target for vaccine development against Dengue. Nowadays, the attention has focused on developing inhibitors based on Papain is a promising target for treating Dengue. In the present work, the theoretical studies of E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and His159) complexes are analysed by Density Functional Theory (M06-2X/cc-pVDZ) method. Among the E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and Hys159) complexes, E-protein(Glu76)…Papain(Cys25) complex has the highest interaction value of −352.22 kcal/mol. Moreover, the natural bond orbital analysis also supports the above results. The 100 ns Molecular Dynamics simulation reveals that, E-protein(Ala54-Ile129)…Papain(Cys25) complex had the lowest root mean square deviation value of 1 Å compared to the E-protein(Ala54-Ile129)… Papain(Asn175 & His159) complexes. The salt bridge formation between the Asp103 and Lys110 residues are the important stabilizing factor in E-protein(Ala54-Ile129)…Papain(Cys25) complex. This result can extend our knowledge of the functional behaviour of Papain and provides structural insight to target Envelope protein as forthcoming drug targets in Dengue.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• Dengue
• molecular dynamics
• papain
• inhibitor
• envelope protein
• salt bridge
• anti-dengue activity

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We are thankful to UGC-BSR Award No: F.25-1/2013-14(BSR)7-307/2010/(BSR) Dated:30.05.2014 for financial assistance. We are also thankful to CMSD (Center for Modelling Simulation and Design) Center of DST Government of India at Hyderabad for providing computational facilities.