Current Strategies for Inhibition of Chikungunya Infection

Abstract

Increasing incidences of Chikungunya virus (CHIKV) infection and co-infections with Dengue/Zika virus have highlighted the urgency for CHIKV management. Failure in developing effective vaccines or specific antivirals has fuelled further research. This review discusses updated strategies of CHIKV inhibition and provides possible future directions. In addition, it analyzes advances in CHIKV lifecycle, drug-target development, and potential hits obtained by in silico and experimental methods. Molecules identified with anti-CHIKV properties using traditional/rational drug design and their potential to succeed in subsequent stages of drug development have also been discussed. Possibilities of repurposing existing drugs based on their in vitro findings have also been elucidated. Probable modes of interference of these compounds at various stages of infection, including entry and replication, have been highlighted. The use of host factors as targets to identify antivirals against CHIKV has been addressed. While most of the earlier antivirals were effective in the early phases of the CHIKV life cycle, this review is also focused on drug candidates that are effective at multiple stages of its life cycle. Since most of these antivirals require validation in preclinical and clinical models, the challenges regarding this have been discussed and will provide critical information for further research.

Phytochemicals as Antiviral Agents: Recent Updates

“…Virus can be inhibited at various stages of its infection ( Fig. 2) (Subudhi et al 2018). Some of the strategies directly inhibit the viral replication by targeting DNA/RNA polymerase, posttranslation modification of viral proteins, or viral assembly (Subudhi et al 2018).…”

“…2) (Subudhi et al 2018). Some of the strategies directly inhibit the viral replication by targeting DNA/RNA polymerase, posttranslation modification of viral proteins, or viral assembly (Subudhi et al 2018). Several mechanisms have been adopted by phytochemicals to inhibit viral replication.…”

A scoping review of Chikungunya virus infection: epidemiology, clinical characteristics, viral co-circulation complications, and control

“…A succinct overview of current strategies for inhibition of CHIKV infection has recently been published (Subudhi et al, 2018). Briefly, among the anti-CHIKV drugs under evaluation, there are preparations that target the viral adsorption and fusion, translation of viral protein and genome replication (mainly in viral non-structural protein 2, nsP2), maturation of viral glycoproteins and immunological molecules (Brighton, 1984;Briolant et al, 2004 Once the molecular test is negative, serological test must be performed.…”

P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages

“…Even though mortality due to CHIKV is very rare and restricted to children's (below 1 year), old age (above 65 years) or immune compromised patients, the pathogenesis (mainly inflammatory responses) may persist for very long periods of time both in humans and macaque model (20,21). Currently, arboviruses raise a serious threat to the global public health, due to unavailability of effective drugs or vaccines (22,23).…”