Chikungunya virus (CHIKV) is the causative agent of chikungunya fever (CHIKF), and its primary vectors are the mosquitoes Aedes aegypti and Aedes albopictus. CHIKV was initially endemic to Africa but has spread globally in recent years and affected millions of people. According to a risk assessment by the World Health Organization, CHIKV has the potential seriously impact public health. A growing body of research suggests that mutations in the CHIKV gene that enhance viral fitness in the host are contributing to the expansion of the global CHIKF epidemic. In this article, we review the host-adapted gene mutations in CHIKV under natural evolution and laboratory transmission conditions, which can help improve our understanding of the adaptive evolution of CHIKV and provide a basis for monitoring and early warning of future CHIKV outbreaks.

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome β5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses’ life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.

Chikungunya fever (CHIKF), which is caused by the Chikungunya virus (CHIKV), has rapidly spread across the globe in recent years, leading to its listing as a public health concern by the World Health Organization. In 2019, the first local outbreak of Asian-type CHIKF was reported in Xishuangbanna, Yunnan Province, China, with 88 CHIKV nucleic acid-positive cases detected from clinical specimens. To further investigate the biological characteristics of the virus strain responsible for this outbreak, we reconstructed the 625D6h strain using reverse genetics and tested its growth kinetics in different cell lines. The results showed a strong replication capacity in the Aedes albopictus C6/36 insect cell line but a weaker one in mammalian cell lines. The virus’s high replication capacity in mosquito cells is an interesting phenotype that warrants further study to determine if it influences vector adaptation and transmission dynamics in endemic settings. The study also found that two DHODH inhibitors, ML390 and vidofludimus, could effectively inhibit CHIKV replication in vitro. The infectious clone created in this study provides a useful tool for studying the recently prevalent Asian-type strain in China, supporting the subsequent development of prevention and treatment methods.

Chikungunya fever (CHIKF) is caused by the Chikungunya virus (CHIKV). In recent years, it has rapidly spread globally and has been listed as a public health concern by the World Health Organization. In 2019, the first local outbreak of Asian-type CHIKF was reported in Xishuangbanna, Yunnan Province, China, with 88 CHIKV nucleic acid-positive cases detected from clinical specimens. To further investigate the biological characteristics of the virus strain responsible for this outbreak, we rescued the 625D6h strain using reverse genetics and tested its growth kinetics in different cell lines. The results showed that the 625D6h strain had strong replication capacity in the Aedes albopictus C6/36 insect cell line but weaker replication capacity in mammalian cell lines. Its high replication capacity under high mosquito vector adaptability may have contributed to the outbreak in 2019. The study also found that two DHODH inhibitors, ML390 and vidofludimus, could effectively inhibit CHIKV replication. The infectious clone created in this study provides a useful tool for studying the recently prevalent Asian-type strain in China and supports the subsequent development of prevention and treatment methods.