Molecular Characterization of DENV-1 Isolates From Pakistan Reveals Immunogenic Variability and Antiviral Potential of Phytochemicals Targeting the CprM Region.

Dengue virus (DENV), a mosquito-borne arbovirus, remains a critical global health concern, causing approximately 390 million infections annually. Dengue fever poses significant challenges to healthcare systems in endemic regions like Pakistan due to the presence of four established serotypes (DENV-1-DENV-4) and the potential emergence of a fifth serotype (DENV-5). The current study aimed to investigate molecular characteristics of DENV-1 isolates from Peshawar, Pakistan, focusing on serotyping, genetic variability in the CprM junction region, and identification of potential antiviral phytochemicals. A total of 45 patient samples were screened, with the highest infection rate (49%) observed among individuals aged 20-40 years. Phylogenetic analysis revealed that six isolates clustered within the DENV-1 clade and grouped closely related to isolates from China, India, Bangladesh, and Pakistan, suggesting a regional evolution and potentially cross-border transmission. The prominent amino acid substitutions were Q47H, G48E, P49H, K51 E/N, L52 M, and M57I, which may influence viral structure, immune evasion, and antigenic properties. To address the lack of effective antivirals, a library of 60 phytochemicals was screened. Nine compounds demonstrated favorable ADMET profiles and high binding affinity (docking scores < -100) with the CprM region. Silydianin exhibited the strongest interaction (-159.81), indicating promising inhibitory potential. This integrative molecular and computational approach enhances our understanding of circulating DENV-1 strains and highlights plant-derived compounds as candidates for future antiviral development, pending in vitro validation.