Aarti Tripathi

West Nile Virus (WNV) belongs to the orthoflavivirus genus and is part of the Flaviviridae family, which includes the Japanese encephalitis virus, Dengue virus, Zika virus, and yellow fever virus. WNV circulates among birds and mosquitoes, posing infection risks to humans and mammals. The significant rise in WNV's geographic spread and infection rates over the past five decades has prompted urgent public health concerns, driving the need for accelerated vaccine research. The development of a vaccine for WNV infection presents several challenges, primarily due to the virus's complex biology, the risk of cross-reactivity with other flaviviruses, safety concerns such as Antibody-dependent enhancement (ADE), and the economic and logistical hurdles in vaccine production. Despite significant research efforts, no human vaccine has been approved, although several candidates are in various stages of development. The current review offers a comprehensive summary of the latest progress and the concomitant challenges in the development of vaccines. It also discusses the role of host-pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis in facilitating the advancement of vaccines.

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy. Extensive research has been conducted in developing effective antivirals for flavivirus. Various approaches have been extensively utilized in clinical trials for antiviral development, targeting virus entry, replication, polyprotein synthesis and processing, and egress pathways exploiting virus as well as host proteins. However, to date, no licensed antiviral drug exists to treat the diseases caused by these viruses. Understanding the mechanisms of host–pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis is highly warranted to foster the development of antivirals. This review provides an extensively detailed summary of the most recent advances in the development of antiviral drugs to combat diseases.