-Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach
Dengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against den...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2023-02-01
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| Series: | Bioinformatics and Biology Insights |
| Online Access: | https://doi.org/10.1177/11779322231158249 |
| _version_ | 1797893435534868480 |
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| author | Dipok Kumer Shill Shafina Jahan Mohammad Mamun Alam Md Belayet Hasan Limon Muntasir Alam Mohammed Ziaur Rahman Mustafizur Rahman |
| author_facet | Dipok Kumer Shill Shafina Jahan Mohammad Mamun Alam Md Belayet Hasan Limon Muntasir Alam Mohammed Ziaur Rahman Mustafizur Rahman |
| author_sort | Dipok Kumer Shill |
| collection | DOAJ |
| description | Dengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against dengue virus serotype 3 (DENV-3) through viroinformatics-based analyses. Since 2017, DENV-3 has been the predominant serotype in Bangladesh. We selected 3 non-structural proteins of DENV-3, named NS3, NS4A, and NS5, as antiviral targets. Protein modeling and validation were performed with VERIFY-3D, Ramachandran plotting, MolProbity, and PROCHECK. We found 4 drug-like compounds from DRUGBANK that can interact with these non-structural proteins of DENV-3. Then, the ADMET profile of these compounds was determined by admetSAR2, and molecular docking was performed with AutoDock, SWISSDOCK, PatchDock, and FireDock. Furthermore, they were subjected to molecular dynamics (MD) simulation study using the DESMOND module of MAESTRO academic version 2021-4 (force field OPLS_2005) to determine their solution’s stability in a predefined body environment. Two drug-like compounds named Guanosine-5’-Triphosphate (DB04137) and S -adenosyl- l -homocysteine (DB01752) were found to have an effective binding with these 3 proteins (binding energy > 33.47 KJ/mole). We found NS5 protein was stable and equilibrated in a 100 ns simulation run along with a negligible (<3Å) root-mean-square fluctuation value. The root-mean-square deviation value of the S -adenosyl- l -homocysteine-NS5 complex was less than 3Å, indicating stable binding between them. The global binding energy of S -adenosyl- l -homocysteine with NS5 was −40.52 KJ/mole as ∆G. Moreover, these 2 compounds mentioned above are non-carcinogenic according to their ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) profile (in silico). These outcomes suggest the suitability of S -adenosyl- l -homocysteine as a potential drug candidate for dengue drug discovery research. |
| first_indexed | 2024-04-10T06:52:55Z |
| format | Article |
| id | doaj.art-7cadf485f332455babff97f9bc547137 |
| institution | Directory Open Access Journal |
| issn | 1177-9322 |
| language | English |
| last_indexed | 2024-04-10T06:52:55Z |
| publishDate | 2023-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Bioinformatics and Biology Insights |
| spelling | doaj.art-7cadf485f332455babff97f9bc5471372023-02-28T08:03:36ZengSAGE PublishingBioinformatics and Biology Insights1177-93222023-02-011710.1177/11779322231158249-Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based ApproachDipok Kumer ShillShafina JahanMohammad Mamun AlamMd Belayet Hasan LimonMuntasir AlamMohammed Ziaur RahmanMustafizur RahmanDengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against dengue virus serotype 3 (DENV-3) through viroinformatics-based analyses. Since 2017, DENV-3 has been the predominant serotype in Bangladesh. We selected 3 non-structural proteins of DENV-3, named NS3, NS4A, and NS5, as antiviral targets. Protein modeling and validation were performed with VERIFY-3D, Ramachandran plotting, MolProbity, and PROCHECK. We found 4 drug-like compounds from DRUGBANK that can interact with these non-structural proteins of DENV-3. Then, the ADMET profile of these compounds was determined by admetSAR2, and molecular docking was performed with AutoDock, SWISSDOCK, PatchDock, and FireDock. Furthermore, they were subjected to molecular dynamics (MD) simulation study using the DESMOND module of MAESTRO academic version 2021-4 (force field OPLS_2005) to determine their solution’s stability in a predefined body environment. Two drug-like compounds named Guanosine-5’-Triphosphate (DB04137) and S -adenosyl- l -homocysteine (DB01752) were found to have an effective binding with these 3 proteins (binding energy > 33.47 KJ/mole). We found NS5 protein was stable and equilibrated in a 100 ns simulation run along with a negligible (<3Å) root-mean-square fluctuation value. The root-mean-square deviation value of the S -adenosyl- l -homocysteine-NS5 complex was less than 3Å, indicating stable binding between them. The global binding energy of S -adenosyl- l -homocysteine with NS5 was −40.52 KJ/mole as ∆G. Moreover, these 2 compounds mentioned above are non-carcinogenic according to their ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) profile (in silico). These outcomes suggest the suitability of S -adenosyl- l -homocysteine as a potential drug candidate for dengue drug discovery research.https://doi.org/10.1177/11779322231158249 |
| spellingShingle | Dipok Kumer Shill Shafina Jahan Mohammad Mamun Alam Md Belayet Hasan Limon Muntasir Alam Mohammed Ziaur Rahman Mustafizur Rahman -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach Bioinformatics and Biology Insights |
| title | -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach |
| title_full | -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach |
| title_fullStr | -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach |
| title_full_unstemmed | -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach |
| title_short | -Adenosyl--Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach |
| title_sort | adenosyl homocysteine exhibits potential antiviral activity against dengue virus serotype 3 denv 3 in bangladesh a viroinformatics based approach |
| url | https://doi.org/10.1177/11779322231158249 |
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