Discovery of Dengue Virus Inhibitors

Abstract

To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors. These studies focused on the structural (C, prM, E) and non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) of dengue virus as well as host factors as drug targets. Hence, this article provides an overall up-to-date review of the discovery of dengue virus inhibitors that are only targeting the structural and non-structural viral proteins as drug targets.

Glycyrrhizic Acid Derivatives Bearing Amino Acid Residues in the Carbohydrate Part as Dengue Virus E Protein Inhibitors: Synthesis and Antiviral Activity

“…It is important that we received some GL conjugates containing amino acid residues included in the active binding sites of the flavivirus’s target proteins such as E-protein, NS2-NS3-proteases, NS3-helicase, and RdRp (Val, Leu, Met, Phe, Tyr, Lys, etc.) [ 16 , 18 , 19 , 20 , 21 , 54 ].…”

“…Among the discovered GL hit derivatives, Compounds 3 and 11 might be chosen as the lead molecules perspective for the development of DENV inhibitors due to the simple synthetic procedure for their preparation and high inhibitory activity against DENV2. The DENV E protein is a key protein of the flavivirus life cycle, playing an important role in virus attachment to the host cell, entry and fusion [ 16 , 18 , 52 ]. It contains three ectodomains and a stem anchor to provide a link to the viral membrane [ 54 ].…”

“…Currently, there are no licensed tetravaccines against all the DENV serotypes, and only one licensed Dengvaxia vaccine is in the pharmaceutical market that protects against DENV1 and DENV2 [ 15 ]. Antiviral drugs for dengue virus-specific chemotherapy are not developed either [ 16 , 17 ]. The following targets are investigated in the search for new antiviral agents against DENV: envelope (E) protein, protease NS2B/NS3, helicase, methyltransferases, RNA-dependent RNA polymerase, R-glucosidase and non-structured proteins [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…NS3 serine-protease plays a key role in the life cycle of DENV and is an ideal target for the design of new antiviral agents [ 21 ]. RNA-dependent RNA polymerase (RdRp) of flaviviruses is used as a target for the development of new antiviral agents and is responsible for initiating and catalyzing the synthesis of viral RNA in the cytoplasm of infected cells [ 12 , 16 ].…”

The Dengue Vaccines: Assessment of Future Prospects, Treatment, and Vaccine Challenges

“…In the initiative of developing a DENV vaccine, Sanofi Pasteur is the furthest one currently [48][49][50][51][52][53][54][55]. The centers for prevention and disease control in the United States have also developed a chimeric dengue vaccine, DENV-axe, which has been licensed to Inviragen, Inc.…”