Molecular Characterization and Computational Analysis of Dengue Virus Serotypes in Peshawar, KPK: Serotype Prevalence, Structural Insights, and Climate-Driven Outbreak Trends

Dengue fever, caused by the dengue virus (DENV) and transmitted by Aedes aegypti, remains a major public health concern in Peshawar, Khyber Pakhtunkhwa (KPK), Pakistan. This study aimed to determine the prevalence of dengue infections, identify dominant serotypes, and predict unsolved protein structures of DENV serotypes through computational modeling. Between July 2018 and November 2023, blood samples from 500 NS1-positive patients at teritary Hospital, Peshawar, were analyzed. Serological testing revealed a 73.2% positivity rate, with DENV2 as the most prevalent serotype (74%), followed by DENV4 (9.78%), DENV3 (8.51%), and DENV1 (7.23%). Age-wise distribution showed the highest burden (37.4%) among 16–30-year-olds. Computational analysis predicted DENV Envelope protein E structures for DENV1, DENV2, and DENV3 using AlphaFold. Physico-chemical analysis confirmed their hydrophilic nature and structural stability, with Q8BE40 (DENV1) and Q7TGD1 (DENV3) exhibiting 91.6% and 91.0% residues in favored regions, respectively. The Flavi Glycoprotein C domain, conserved across all three serotypes, contained one active binding site, interacting with key residues (GLN, HIS, GLY, THR, ARG, GLU, LYS). Molecular docking identified Lenacapavir as the most effective ligand for Q8BE40 (DENV1), offering potential antiviral targets.The findings highlight DENV2 dominance, structural adaptations, and climate-driven outbreak patterns, emphasizing the need for enhanced surveillance, climate-adaptive vector control, and antiviral development to mitigate the increasing dengue burden in Pakistan.