E2 Protein of Chikungunya Virus: A Narrative Review of Its Potential as a Therapeutic Target

Introduction: Chikungunya Virus (CHIKV), an enveloped RNA virus transmitted by Aedes mosquitoes, has become an increasing global health concern, particularly in South America, where cases and fatalities have risen (PAHO, 2023). This review focuses on therapeutic strategies targeting the CHIKV E2 protein, including vaccines, antibodies, and antiviral approaches tested in vitro and in vivo. Methods: Literature reporting on the E2 protein, including studies on viral structure, host interactions, symptoms, and treatments under development, was analyzed. Results: The E2 protein, a major structural component of CHIKV, is critical for viral entry and virulence, mediating interactions with host factors (Glycosaminoglycans (GAGs) and C-type lectins) and receptors (Matrix Remodeling-Associated Protein 8 (Mxra8) and Prohibitin-1 (PHB1)). It also elicits robust antibody responses, making it a key target for therapeutic intervention. Discussion: The E2 protein is essential for CHIKV entry and virulence, making it a key target for vaccines, antibodies, and antivirals. While preclinical studies show promise, efficacy varies and clinical translation remains limited. Challenges include viral diversity, immune escape, and the need for integrated strategies combining different therapeutic approaches. Conclusion: Given the absence of licensed vaccines and antivirals for alphaviruses, the E2 protein represents a promising therapeutic target while inhibiting E2 could block viral entry and infection. However, current strategies show variable efficacy and inconclusive results, highlighting the need for further research to validate and optimize E2-targeted therapies.