Peptides as Therapeutic Agents for Dengue Virus

Abstract

Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients.

Keywords: Antiviral therapeutics.; Dengue virus; Drug discovery; Peptides.

Figure 1

Schematic diagram of the DENV genome showing structural and non-structural polyproteins that are encoded by the DENV genome.

Figure 2

Schematic diagram of DENV replication cycle and summary of antiviral peptides. The antiviral peptides are classified according to their mechanism of actions, which include entry inhibitors, fusion inhibitors, translation inhibitors and replication inhibitors.

Figure 3

Schematic diagram of DENV envelope (E) proteins in their dimeric forms.