Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis
Abstract COVID-19 has proved to be a global health crisis during the pandemic, and the emerging JN.1 variant is a potential threat. Therefore, finding alternative antivirals is of utmost priority. In the current report, we present the synthesis of new and potential anti-viral pyrazoline compounds. H...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-81711-5 |
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| author | Rekha Joshi Harsh Gaikwad Bhavana Soge Abdulrahman Alshammari Norah A. Albekairi Atul Kabra Usha Yashwante Baban Kolte Pradip Lokhande Rohan J Meshram |
| author_facet | Rekha Joshi Harsh Gaikwad Bhavana Soge Abdulrahman Alshammari Norah A. Albekairi Atul Kabra Usha Yashwante Baban Kolte Pradip Lokhande Rohan J Meshram |
| author_sort | Rekha Joshi |
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| description | Abstract COVID-19 has proved to be a global health crisis during the pandemic, and the emerging JN.1 variant is a potential threat. Therefore, finding alternative antivirals is of utmost priority. In the current report, we present the synthesis of new and potential anti-viral pyrazoline compounds. Here we report a chemical scheme where β-aryl β-anilino ketones react with phenyl hydrazine in potassium hydroxide to give the corresponding 3,5-diarylpyrazoline. The protocol is applicable to a variety of β-amino ketones and tolerates several functional groups. This method is efficient and proceeds regioselectivity since the β-Anilino group acts as a protecting group for alkenes of chalcones. We identified the NSP3-microdomain (Mac-1) of SARS-CoV-2 as a putative target for newly synthesized triaryl-2-pyrazoline compounds. The molecular dynamics simulation-based free energy estimation suggests compounds 7a, 7d, 7 g, 7i, 7k, and 7 L as promising Mac-1 inhibitors. The detailed structural inspection of MD simulation trajectories sheds light on the structural and functional dynamics involved in the SARS-CoV-2 Mac-1. The data presented here is expected to guide the design and development of better anti-SARS-CoV-2 therapies. |
| format | Article |
| id | doaj-art-09819de710cb4b5297944c09f831a0ec |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-09819de710cb4b5297944c09f831a0ec2025-01-05T12:15:25ZengNature PortfolioScientific Reports2045-23222025-01-0115113110.1038/s41598-024-81711-5Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysisRekha Joshi0Harsh Gaikwad1Bhavana Soge2Abdulrahman Alshammari3Norah A. Albekairi4Atul Kabra5Usha Yashwante6Baban Kolte7Pradip Lokhande8Rohan J Meshram9Department of Chemistry, Savitribai Phule Pune University, PuneDepartment of Chemistry, Savitribai Phule Pune University, PuneBioinformatics Centre, Savitribai Phule Pune UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityUniversity Institute of Pharma Sciences, Chandigarh UniversityBioinformatics Centre, Savitribai Phule Pune UniversityDepartment of Microbial Genome Research, Leibniz Institute DSMZ – German Collection of Microorganisms and Cell CulturesDepartment of Chemistry, Savitribai Phule Pune University, PuneBioinformatics Centre, Savitribai Phule Pune UniversityAbstract COVID-19 has proved to be a global health crisis during the pandemic, and the emerging JN.1 variant is a potential threat. Therefore, finding alternative antivirals is of utmost priority. In the current report, we present the synthesis of new and potential anti-viral pyrazoline compounds. Here we report a chemical scheme where β-aryl β-anilino ketones react with phenyl hydrazine in potassium hydroxide to give the corresponding 3,5-diarylpyrazoline. The protocol is applicable to a variety of β-amino ketones and tolerates several functional groups. This method is efficient and proceeds regioselectivity since the β-Anilino group acts as a protecting group for alkenes of chalcones. We identified the NSP3-microdomain (Mac-1) of SARS-CoV-2 as a putative target for newly synthesized triaryl-2-pyrazoline compounds. The molecular dynamics simulation-based free energy estimation suggests compounds 7a, 7d, 7 g, 7i, 7k, and 7 L as promising Mac-1 inhibitors. The detailed structural inspection of MD simulation trajectories sheds light on the structural and functional dynamics involved in the SARS-CoV-2 Mac-1. The data presented here is expected to guide the design and development of better anti-SARS-CoV-2 therapies.https://doi.org/10.1038/s41598-024-81711-5Regioselective synthesisNSP3-macrodomainCOVID-omicron XBB variantDockingMMPBSALinear interaction energy |
| spellingShingle | Rekha Joshi Harsh Gaikwad Bhavana Soge Abdulrahman Alshammari Norah A. Albekairi Atul Kabra Usha Yashwante Baban Kolte Pradip Lokhande Rohan J Meshram Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis Scientific Reports Regioselective synthesis NSP3-macrodomain COVID-omicron XBB variant Docking MMPBSA Linear interaction energy |
| title | Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis |
| title_full | Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis |
| title_fullStr | Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis |
| title_full_unstemmed | Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis |
| title_short | Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis |
| title_sort | exploring pyrazolines as potential inhibitors of nsp3 macrodomain of sars cov 2 synthesis and in silico analysis |
| topic | Regioselective synthesis NSP3-macrodomain COVID-omicron XBB variant Docking MMPBSA Linear interaction energy |
| url | https://doi.org/10.1038/s41598-024-81711-5 |
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