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In the search for natural therapeutic alternatives against WSSV, this study explored the antiviral potential of portoamides, natural peptides produced by the cyanobacterium <jats:italic>Phormidium<\/jats:italic> sp. LEGE 05292. Given that the structural proteins of the viral envelope, specifically VP28, VP26, and VP24, are the primary mediators of host cell attachment, they serve as promising targets for antiviral drug development. Our approach combined <jats:italic>in vivo<\/jats:italic> post-infection histopathological analysis with <jats:italic>in silico<\/jats:italic> molecular docking to assess the antiviral efficacy of portoamides. In the <jats:italic>in vivo<\/jats:italic> study, crabs were injected with portoamides alongside WSSV and monitored for 30 days post-infection. The antiviral activity of portoamides was evaluated through survival rates and histopathological observations. The results revealed that crabs treated with portoamides showed improved survival and reduced signs of viral infection compared to the control group. In parallel, <jats:italic>in silico<\/jats:italic> molecular docking analysis was conducted to assess the binding affinity between portoamides and the viral envelope proteins VP28, VP26, and VP24. The docking results demonstrated that these proteins exhibited the highest binding energies with portoamides, indicating a strong interaction that could potentially inhibit viral attachment and replication. Our findings suggest that portoamides effectively inhibit WSSV replication by interacting with the viral envelope proteins, thereby preventing the virus from establishing infection in crabs. Moreover, it is hypothesized that portoamides may stimulate the immune system in crabs, further enhancing resistance to WSSV infection. However, additional studies are needed to fully understand the immunomodulatory mechanisms involved. These preliminary results highlight the potential of portoamides as natural antiviral agents for combating WSSV in aquaculture settings, paving the way for future research on their application in disease management strategies.\n<\/jats:p>","DOI":"10.1007\/s10499-025-01947-4","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T23:16:35Z","timestamp":1743894995000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In vivo and in silico preliminary evaluation of the cyanobacterial peptides portoamides A and B against the white spot syndrome virus in freshwater crabs (Paratelphusa hydrodomous)"],"prefix":"10.1007","volume":"33","author":[{"given":"Bharath","family":"Raja","sequence":"first","affiliation":[]},{"given":"Vidya","family":"Radhakrishnan","sequence":"additional","affiliation":[]},{"given":"Sudhakaran","family":"Raja","sequence":"additional","affiliation":[]},{"given":"Sandra","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Vitor","family":"Vasconcelos","sequence":"additional","affiliation":[]},{"given":"Mariana","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Joana R.","family":"Almeida","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"1947_CR1","doi-asserted-by":"publisher","first-page":"354","DOI":"10.3390\/MD15110354","volume":"15","author":"SA Ali Shah","year":"2017","unstructured":"Ali Shah SA, Akhter N, Auckloo BN, Khan I, Lu Y, Wang K, Wu B, Guo YW (2017) Structural diversity, biological properties and applications of natural products from cyanobacteria. 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