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<p>Dengue virus (DENV) predominantly affects tropical and subtropical regions. The growing incidence of DENV infections highlights the critical need to develop novel antiviral therapies. Proteases are essential factors in the life cycles of numerous pathogenic viruses, exerting a crucial influence on viral replication. The selective inhibition of these enzymes represents a promising strategy for antiviral drug development against such pathogens. Our study aimed to isolate and characterize a protease inhibitor (PI) with activity against the DENV, highlighting hot spring actinomycetes as a promising source of antiviral compounds. We successfully identified a potent isolate, <i>Streptomyces sp.</i> by exploring a previously under-studied ecological niche in the Rajgir hot springs. VITARB4 (Accession No.PQ339659) plate assay method and quantitative assessments of protease inhibition revealed <i>Streptomyces</i> sp. VITARB4 produces a strong inhibitor of cysteine proteases. Further analysis using UPLC, GC-MS, and FTIR identified diethyl phthalate as the key compound responsible for the observed protease inhibitory activity. Molecular docking of diethyl phthalate with the NS5 protein demonstrated high binding affinity and significant interactions, indicating potential effectiveness against this target protein. Subsequent assessment of its drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties demonstrated favorable pharmacokinetic characteristics, highlighting its potential as a promising therapeutic agent.</p> Graphical Abstract <p></p>

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Unraveling the anti-dengue viral potential of protease inhibitors from Streptomyces spp.

  • 期刊论文

  • 发表日期：

    2025年4月16日

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  • Aparana Kumari,
  • Kokati Venkata Bhaskara Rao

摘要

Dengue virus (DENV) predominantly affects tropical and subtropical regions. The growing incidence of DENV infections highlights the critical need to develop novel antiviral therapies. Proteases are essential factors in the life cycles of numerous pathogenic viruses, exerting a crucial influence on viral replication. The selective inhibition of these enzymes represents a promising strategy for antiviral drug development against such pathogens. Our study aimed to isolate and characterize a protease inhibitor (PI) with activity against the DENV, highlighting hot spring actinomycetes as a promising source of antiviral compounds. We successfully identified a potent isolate, Streptomyces sp. by exploring a previously under-studied ecological niche in the Rajgir hot springs. VITARB4 (Accession No.PQ339659) plate assay method and quantitative assessments of protease inhibition revealed Streptomyces sp. VITARB4 produces a strong inhibitor of cysteine proteases. Further analysis using UPLC, GC-MS, and FTIR identified diethyl phthalate as the key compound responsible for the observed protease inhibitory activity. Molecular docking of diethyl phthalate with the NS5 protein demonstrated high binding affinity and significant interactions, indicating potential effectiveness against this target protein. Subsequent assessment of its drug-likeness and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties demonstrated favorable pharmacokinetic characteristics, highlighting its potential as a promising therapeutic agent.

Graphical Abstract