New insights into therapeutic strategies against Zika virus from virus–host interactions

Global climate change has created favorable conditions for the transmission and expansion of the Zika virus (ZIKV), with the risk of ZIKV re-emergence posing an ongoing biosecurity threat. However, the lack of effective anti-Zika drugs makes the clinical application of symptom-relieving therapies the only available option. Recent progress in understanding virus–host interactions has significantly accelerated the development of innovative antiviral strategies against ZIKV infection. This review examines the challenges encountered in the development of anti-ZIKV drugs and explores potential therapeutic strategies through a novel ZIKV–host interaction perspective. Moreover, this review systematically outlines novel anti-ZIKV drug strategies, including promising molecular mechanisms and potential targets derived from ZIKV, replication-associated host factors, and immune system elements for drug design. Targeting ZIKV structural components to disrupt its life cycle remains a conventional antiviral strategy, while targeting replication-associated host factors and developing drugs that modulate host cellular processes represent promising therapeutic approaches. The frequently neglected antagonistic effect of ZIKV on innate host immunity and corresponding antiviral strategies are also examined in this review. More importantly, recent progress in antiviral strategies during pregnancy and anti-ZIKV drug delivery strategies are examined, with a focus on potential challenges and future directions for anti-Zika drugs. Further, regulating key placental blood barrier targets represents a promising therapeutic strategy against ZIKV during pregnancy. The progress of anti-ZIKV drug delivery systems enable maximum therapeutic efficacy. This review proposes an integration of potential intervention strategies from the perspective of ZIKV–host interactions, thereby aiming to establish a foundation for future anti-ZIKV research while accelerating the translation of anti-ZIKV therapeutics into clinical practice.