The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies

Abstract

Chikungunya virus (CHIKV) has re-emerged as one of the many medically important arboviruses that have spread rampantly across the world in the past decade. Infected patients come down with acute fever and rashes, and a portion of them suffer from both acute and chronic arthralgia. Currently, there are no targeted therapeutics against this debilitating virus. One approach to develop potential therapeutics is by understanding the viral-host interactions. However, to date, there has been limited research undertaken in this area. In this review, we attempt to briefly describe and update the functions of the different CHIKV proteins and their respective interacting host partners. In addition, we also survey the literature for other reported host factors and pathways involved during CHIKV infection. There is a pressing need for an in-depth understanding of the interaction between the host environment and CHIKV in order to generate potential therapeutics.

Target Identification Using Homopharma and Network-Based Methods for Predicting Compounds Against Dengue Virus-Infected Cells

“…Moreover, it has been reported to have an antiviral role in infection with HIV and some flaviviruses [19,66]. Recently, a KAT5 inhibitor was shown to have an inhibitory effect against the Chikungunya virus, at the step of viral replication with a therapeutic index of 4.65 [19], and against HCV [20,23].…”

“…The liquid from a cashew nutshell (Anacardium occidentale) consists of various phenolic lipid compounds, including anacardic acid, cardol, and cardanol. Previous reports suggested that their biological activities include anti-oxidant, anti-cancer, anti-inflammation, anti-microbial and anti-viral properties [19][20][21][22][23]. Mixed anacardic acid was demonstrated to have potential compound to inhibit Hepatitis C virus (HCV) life cycle [23], and may act through perturbation of the host target at lysine acetyltransferase 5 (KAT5 or TIP60), which is involved in viral replication [19,20].…”

“…Previous reports suggested that their biological activities include anti-oxidant, anti-cancer, anti-inflammation, anti-microbial and anti-viral properties [19][20][21][22][23]. Mixed anacardic acid was demonstrated to have potential compound to inhibit Hepatitis C virus (HCV) life cycle [23], and may act through perturbation of the host target at lysine acetyltransferase 5 (KAT5 or TIP60), which is involved in viral replication [19,20]. Recently, cardol triene was reported to inhibit all dengue serotypes, and molecular dynamics simulation and cell-based functional assays suggested the potential target of this compound is the kl-loop of the DENV envelope (E) protein [21].…”

Small Molecule Inhibitors Targeting Chikungunya Virus

“…The nsP1 protein is a viral mRNA capping enzyme with both methyltransferase and guanylyltransferase (GTase) activities. The protein is responsible for capping and methylation of new synthesized viral RNA protecting it from degradation by host exonucleases and directing efficient translation of viral mRNAs (Rupp et al 2015;Wong and Chu 2018). Additionally, nsP1 plays an important role in RC formation and localization, which is directed by an alpha-helical amphipathic loop and palmitoylation site that allows nsP1 containing RCs to dock to the host cell plasma membrane.…”

“…(2) nucleotide triphosphatase (NTPase) activity; (3) RNA 5′ triphosphatase activity; and (4) papain-like cysteine protease activity (Rupp et al 2015;Wong and Chu 2018;Das et al 2014b;Karpe et al 2011;Ramakrishnan et al 2017). Activity of the C-terminal protease domain is responsible for processing the viral nsP1234 polyprotein (Ramakrishnan et al 2017).…”