Highlights•Reviews on unsolved issues of DENV from different perspectives such as the effect of antibody dependent enhancement, immune escape and limitations of commercial diagnostic kits.•Case studies on variety of potential therapeutic candidates targeting on DENV such as peptide inhibitors, broadly neutralizing antibodies, engineered antibody, vaccine candidates and antiviral agents.•Exploring different approaches for the improvisation of DENV diagnosis such as application of bio-functionalized tapered optical fiber, nanobody derivatives and antibody engineering.