Structure‐Based Design and ADME Screening of Benzimidazole Derivatives as Potential Therapeutics for Human Metapneumovirus (HMPV) (ICSEM 2025)

Human metapneumovirus (HMPV) remains a significant challenge in respiratory healthcare, primarily due to the lack of targeted antiviral therapies and vaccines. In this study, six new benzimidazole derivatives ( M1–M6 ) were synthesized and characterized using FT–IR and 1 H‐NMR techniques. These compounds showed potential activity against the RNA‐dependent RNA polymerase enzyme of HMPV. To evaluate benzimidazole and its six derivatives as potential polymerase inhibitors, in silico molecular docking studies were performed. The results indicated that the effectiveness of compounds ( M1–M6 ) is comparable to MRK‐1 , a synthetic non‐nucleoside inhibitor of the polymerase that blocks conformational changes necessary for the enzyme to initiate RNA synthesis and transition into the elongation phase. Among the tested compounds, M1 , M4 , and M5 demonstrated the most favorable binding energies with the protein 8FPJ (−5.270, −5.406, and −5.622 kcal/mol, respectively), whereas MRK‐1 showed a binding energy of −8.471 kcal/mol. Compounds M2 , M3 , and M6 also exhibited good binding affinities (−6.477, −6.819, and −6.480 kcal/mol, respectively). Pharmacokinetic and toxicity analyses further supported the potential candidacy of these compounds as antiviral agents targeting the RNA‐dependent RNA polymerase enzyme.