Designing of nanobodies against Dengue virus Capsid: a computational affinity maturation approach

Abstract

Dengue virus, an arbovirus, is one of the most prevalent diseases in the tropical environment and leads to huge number of casualties every year. No therapeutics are available till date against the viral disease and the only medications provide symptomatic relief. In this study, we have focused on utilizing conventional nanobodies and repurposing them for Dengue. Computationally affinity matured, best binding nanobodies tagged with constant antibody regions, could be proposed as therapeutics. These could also be applied for drug delivery purposes due to their high specificity against the viral Capsid. Another application of these nanobodies has been thought to utilize them for diagnostic purposes, to use the nanobodies for viral detection from patient samples at the earliest stage using ELISA. This study may open a new avenue for immunologic study in foreseeable future with the usage of the same molecules for multiple purposes.

Highlights

• Natural nanobodies against viruses were modified for use against Dengue virus Capsid conserved regions.

• Computational affinity maturation was performed making use of change in binding affinities upon mutating various residues in the complementary determining regions.

• Docking studies performed to inspect the docking groove, interface analysis and energy calculations.

• MM/GBSA calculations done to calculate binding free energy of the complex to determine stability of the complex.

Communicated by Ramaswamy H. Sarma

Keywords:

• Nanobodies
• Dengue virus Capsid
• computational affinity maturation
• MD simulation
• MM/PBSA

Disclosure statement

The authors declare no conflict of interest.

Funding

The author(s) reported there is no funding associated with the work featured in this article.