Drugs targeting structural and nonstructural proteins of the chikungunya virus: A review.

Chikungunya virus (CHIKV) is a single positive-stranded RNA virus of the Togaviridae family and Alphavirus genus, with a typical lipid bilayer envelope structure, and is the causative agent of human chikungunya fever (CHIKF). The U.S. Food and Drug Administration has recently approved the first chikungunya vaccine, Ixchiq; however, vaccination rates are low, and CHIKF is prevalent owing to its periodic outbreaks. Thus, developing effective anti-CHIKV drugs in clinical settings is imperative. Viral proteins encoded by the CHIKV genome play vital roles in all stages of infection, and developing therapeutic agents that target these CHIKV proteins is an effective strategy to improve CHIKF treatment efficacy and reduce mortality rates. Therefore, in the present review article, we aimed to investigate the basic structure, function, and replication cycle of CHIKV and comprehensively outline the current status and future advancements in anti-CHIKV drug development, specifically targeting nonstructural (ns) proteins, including nsP1, nsP2, nsP3, and nsP4 and structural proteins such as capsid (C), E3, E2, 6K, and E1.

Uncovering chikungunya virus-encoded miRNAs and host-specific targeted genes associated with antiviral immune responses: an integrated bioinformatics approach.

Chikungunya virus (CHIKV) is a single-stranded RNA virus belonging to the genus Alphavirus and is responsible for causing Chikungunya fever, a type of arboviral fever. Despite extensive research, the pathogenic mechanism of CHIKV within host cells remains unclear. In this study, an in-silico approach was used to predict that CHIKV produces micro-RNAs that target host-specific genes associated with host cellular regulatory pathways. Putative micro-RNAs of CHIKV were predicted using the miRNAFold and Vmir RNA structure web servers, and secondary structure prediction was performed using RNAfold. Host-specific target genes were then predicted, and hub genes were identified using CytoHubba and module selection through MCODE. Functional annotations of hub genes revealed their association with various pathways, including osteoclast differentiation, neuroactive ligand-receptor interaction, and mRNA surveillance. We used the freely available dataset GSE49985 to determine the level of expression of host-specific target genes and found that two genes, F-box and leucine-rich repeat protein 16 (FBXL16) and retinoic acid receptor alpha (RARA), were down-regulated, while four genes, RNA binding protein with serine-rich domain 1 (RNPS1), RNA helicase and ATPase (UPF1), neuropeptide S receptor 1 (NPSR1), and vasoactive intestinal peptide receptor 1 (VIPR1), were up-regulated. These findings provide insight into novel miRNAs and hub genes associated with CHIKV infection and suggest potential targets for therapeutic intervention. Further experimental validation of these targets could lead to the development of effective treatments for CHIKV-mediated diseases.