Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections: In silico vs. In vitro approach

Abstract

An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.

Synthesis and biological activity of imidazole phenazine derivatives as potential inhibitors for NS2B-NS3 dengue protease

“…Therefore, it is suggested that having more interaction with the residue will lead to a better result in the inhibitory activity. Furthermore, to create the stable energy-favored ligands at the interface of a protein structure and alter the binding affinity for the drug efficacy, it was crucial to observe the hydrogen bonding and optimize the hydrophobic interactions [ 48 ]. It was found that both 3e and 3k showed more hydrogen bonding interactions with NS2B-NS3pro compared to quercetin ( Table 4 ).…”

Antiviral Activities of Streptomyces KSF 103 Methanolic Extracts against Dengue Virus Type-2

“…Previous studies have shown that the level of viremia in dengue patients corresponds to the severity of the disease [ 5 , 11 ]. The viremia level was higher in secondary dengue infection, which may prolong the disease and increase the chances of manifesting severe dengue symptoms [ 5 , 11 , 12 , 13 , 14 ]. Treatments such as antivirals to reduce the level of viremia, hence, could possibly reduce the severity of dengue.…”

“…Various strategies are being explored to hinder the replication of the dengue virus, including targeting the NS3 protease, NS5 polymerase, and virus entry process. The NS3 protease plays a vital role in viral replication, and inhibiting this enzyme could disrupt the virus’s life cycle [ 10 , 12 , 13 , 14 ]. Several compounds have demonstrated promise in inhibiting the NS3 protease during preclinical studies [ 10 , 12 , 13 , 14 ].…”

“…The NS3 protease plays a vital role in viral replication, and inhibiting this enzyme could disrupt the virus’s life cycle [ 10 , 12 , 13 , 14 ]. Several compounds have demonstrated promise in inhibiting the NS3 protease during preclinical studies [ 10 , 12 , 13 , 14 ]. The NS5 polymerase, another crucial enzyme involved in viral replication, is also being targeted as a potential avenue to prevent viral replication [ 10 , 16 , 17 ].…”

The Antiviral Activity of Varenicline against Dengue Virus Replication during the Post-Entry Stage

“…Phytochemicals including fatty acids, glucosides, terpenes, flavonoids, phenolics, chalcones, acetamides, and peptides have shown potential as inhibitors of DENV, with curcumin, quercetin, and myricetin acting as noncompetitive inhibitors of the NS2b-NS3 protease enzyme [9]. In silico and in vitro studies have provided ample phytochemical hits for the experimental assessment of their use as DENV protease inhibitors [10], indicating that natural product derivatives can be designed and synthesized to enhance specificity and efficacy toward these proteases.…”