Potential inhibitors isolated from Curcuma aeruginosa against dengue virus type 2 (DENV-2) NS2B-NS3 protease activity
Dengue virus (DENV) infection remains a formidable public health concern, causing significant fatalities worldwide. The unavailability of specific anti-DENV therapeutics and poor response towards dengue vaccine have impeded efforts to prevent and control this tropical disease, thereby, there is a pr...
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Published in | Journal of biologically active products from nature Vol. 14; no. 1; pp. 64 - 79 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
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Taylor & Francis
02.01.2024
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Abstract | Dengue virus (DENV) infection remains a formidable public health concern, causing significant fatalities worldwide. The unavailability of specific anti-DENV therapeutics and poor response towards dengue vaccine have impeded efforts to prevent and control this tropical disease, thereby, there is a pressing need for effective alternative therapeutics. Curcuma species including Curcuma aeruginosa have a long history of traditional use for the prevention and treatment of various ailments, including viral infections. While it is evident that several compounds isolated from these plants have antiviral activity against various viruses, their specific effects against DENV have not been thoroughly explored. The study aimed to investigate the potential of major compounds isolated from C. aeruginosa (demethoxycurcumin, curcumenol, furanodienone germacrone and zederone) in inhibiting DENV-2 NS2B-NS3 protease activity both in vitro and in silico. The results demonstrated that demethoxycurcumin (at 100 μM), furanodienone and germacrone (both at 25 μM) exhibited inhibitory effects on NS2B-NS3 protease activity comparable to aprotinin, a potent NS2B-NS3 protease inhibitor, albeit to a lesser extent. Importantly, these inhibitory concentrations did not adversely affect the viability of normal fibroblast cell line, L-929 cells, suggesting that the compounds' effects were specific to the protease inhibition. Further in silico molecular docking analyses indicated that demethoxycurcumin, furanodienone and germacrone displayed significant binding affinities with both DENV E protein and DENV NS2B-NS3 protease, corroborating their inhibitory activity observed in the protease inhibition assay. These promising findings collectively suggest that demethoxycurcumin, furanodienone and germacrone from C. aeruginosa merit further development as distinctive inhibitors for treating DENV infection. |
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AbstractList | Dengue virus (DENV) infection remains a formidable public health concern, causing significant fatalities worldwide. The unavailability of specific anti-DENV therapeutics and poor response towards dengue vaccine have impeded efforts to prevent and control this tropical disease, thereby, there is a pressing need for effective alternative therapeutics. Curcuma species including Curcuma aeruginosa have a long history of traditional use for the prevention and treatment of various ailments, including viral infections. While it is evident that several compounds isolated from these plants have antiviral activity against various viruses, their specific effects against DENV have not been thoroughly explored. The study aimed to investigate the potential of major compounds isolated from C. aeruginosa (demethoxycurcumin, curcumenol, furanodienone germacrone and zederone) in inhibiting DENV-2 NS2B-NS3 protease activity both in vitro and in silico. The results demonstrated that demethoxycurcumin (at 100 μM), furanodienone and germacrone (both at 25 μM) exhibited inhibitory effects on NS2B-NS3 protease activity comparable to aprotinin, a potent NS2B-NS3 protease inhibitor, albeit to a lesser extent. Importantly, these inhibitory concentrations did not adversely affect the viability of normal fibroblast cell line, L-929 cells, suggesting that the compounds' effects were specific to the protease inhibition. Further in silico molecular docking analyses indicated that demethoxycurcumin, furanodienone and germacrone displayed significant binding affinities with both DENV E protein and DENV NS2B-NS3 protease, corroborating their inhibitory activity observed in the protease inhibition assay. These promising findings collectively suggest that demethoxycurcumin, furanodienone and germacrone from C. aeruginosa merit further development as distinctive inhibitors for treating DENV infection. |
Author | Al-Amin, Mohammad Zakaria, Iffah Izzati Kahar, Ummirul Mukminin Mohtar, Noratiqah Salhimi, Salizawati Muhamad Fazalul Rahiman, Siti Sarah Khairuddean, Melati |
Author_xml | – sequence: 1 givenname: Siti Sarah surname: Fazalul Rahiman fullname: Fazalul Rahiman, Siti Sarah organization: Universiti Sains Malaysia – sequence: 2 givenname: Mohammad surname: Al-Amin fullname: Al-Amin, Mohammad organization: Universiti Sains Malaysia – sequence: 3 givenname: Noratiqah surname: Mohtar fullname: Mohtar, Noratiqah organization: Universiti Sains Malaysia – sequence: 4 givenname: Iffah Izzati surname: Zakaria fullname: Zakaria, Iffah Izzati organization: Malaysia Genome and Vaccine Institute, National Institutes of Biotechnology Malaysia – sequence: 5 givenname: Ummirul Mukminin surname: Kahar fullname: Kahar, Ummirul Mukminin organization: Malaysia Genome and Vaccine Institute, National Institutes of Biotechnology Malaysia – sequence: 6 givenname: Melati surname: Khairuddean fullname: Khairuddean, Melati organization: Universiti Sains Malaysia – sequence: 7 givenname: Salizawati Muhamad surname: Salhimi fullname: Salhimi, Salizawati Muhamad email: saliza@usm.my organization: Universiti Sains Malaysia |
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Snippet | Dengue virus (DENV) infection remains a formidable public health concern, causing significant fatalities worldwide. The unavailability of specific anti-DENV... |
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SubjectTerms | Curcuma dengue DENV-2 NS2B-NS3 molecular docking protease inhibitor |
Title | Potential inhibitors isolated from Curcuma aeruginosa against dengue virus type 2 (DENV-2) NS2B-NS3 protease activity |
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