Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies
Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2, have caused global epidemics with high morbidity and mortality. Active research on finding effective drugs against 2019-nCoV/SARS-CoV-2 is...
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| Format: | Article |
| Language: | English |
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Sciendo
2023-04-01
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| Series: | The EuroBiotech Journal |
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| Online Access: | https://doi.org/10.2478/ebtj-2023-0009 |
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| author | Madishetti Vinuthna Vani Reddy Sudhakar kalagara Sudhakar Garg Ashish Enaganti Sreenivas Hussain Sardar |
| author_facet | Madishetti Vinuthna Vani Reddy Sudhakar kalagara Sudhakar Garg Ashish Enaganti Sreenivas Hussain Sardar |
| author_sort | Madishetti Vinuthna Vani |
| collection | DOAJ |
| description | Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2, have caused global epidemics with high morbidity and mortality. Active research on finding effective drugs against 2019-nCoV/SARS-CoV-2 is going on. In silico screening represents the best approach for hits identification and could shorten the time and reduce cost compared to de novo drug discovery. Recently, CoV2 mutations have been a big concern in India, particularly on non-structural proteins (NSPs) and Spike Protein (B.1.617) which are the key targets that play a pivotal role in mediating viral replication and transcription. Herein, this study analyzed the NSPs and spike’s structural aspects of mutant strains of SARS-CoV-2. The three-dimensional structures of NSPs and S Spike proteins were retrieved from the protein data bank or modeled. And a dataset of an antiviral compound library containing 490,000 drug-like ligands and structurally diverse biologically active scaffolds was used for our studies. Initially, the molecular alignment was performed for library compounds with the reference drug molecule to find targets that match the field points. Antiviral compounds having a similarity score >0.6; were selected for further docking studies with wild and mutant NSPs and S Spike protein of SARS-CoV-2 variant B.1.617. The docking studies identified a potent analog MA-11, which exhibited the highest binding affinity towards wild and mutant proteins. Further, molecular dynamics simulation studies of selected compounds confirmed their perfect fitting into NSP12 and spike active sites and offer direction for further lead optimization and rational drug design. |
| first_indexed | 2024-04-09T14:08:09Z |
| format | Article |
| id | doaj.art-e3e888ef10074d1da25cb1841f6d31a7 |
| institution | Directory Open Access Journal |
| issn | 2564-615X |
| language | English |
| last_indexed | 2024-04-09T14:08:09Z |
| publishDate | 2023-04-01 |
| publisher | Sciendo |
| record_format | Article |
| series | The EuroBiotech Journal |
| spelling | doaj.art-e3e888ef10074d1da25cb1841f6d31a72023-05-06T15:58:55ZengSciendoThe EuroBiotech Journal2564-615X2023-04-017213214310.2478/ebtj-2023-0009Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation StudiesMadishetti Vinuthna Vani0Reddy Sudhakar1kalagara Sudhakar2Garg Ashish3Enaganti Sreenivas4Hussain Sardar5Department of Bioinformatics, Averinbiotech laboratories, 208, 2nd Floor, Windsor Plaza, Nallakunta, Hyderabad, Telangana, India.2University of Massachusetts Chan medical school, RNA therapeutics institute, Worcester, Massachusetts, USA, 01655.3Department of chemistry and biochemistry, University of the Texas at El Paso, 500 W University Ave, El paso TX 79968.4Department of PG Studies and Research in Chemistry and Pharmacy, Rani Durgavati University, Jabalpur, MP, India 482003.Department of Bioinformatics, Averinbiotech laboratories, 208, 2nd Floor, Windsor Plaza, Nallakunta, Hyderabad, Telangana, India.6Department of Biotechnology, Government Science College, Chitradurga, Karnataka, India.Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV), also known as SARS-CoV-2, have caused global epidemics with high morbidity and mortality. Active research on finding effective drugs against 2019-nCoV/SARS-CoV-2 is going on. In silico screening represents the best approach for hits identification and could shorten the time and reduce cost compared to de novo drug discovery. Recently, CoV2 mutations have been a big concern in India, particularly on non-structural proteins (NSPs) and Spike Protein (B.1.617) which are the key targets that play a pivotal role in mediating viral replication and transcription. Herein, this study analyzed the NSPs and spike’s structural aspects of mutant strains of SARS-CoV-2. The three-dimensional structures of NSPs and S Spike proteins were retrieved from the protein data bank or modeled. And a dataset of an antiviral compound library containing 490,000 drug-like ligands and structurally diverse biologically active scaffolds was used for our studies. Initially, the molecular alignment was performed for library compounds with the reference drug molecule to find targets that match the field points. Antiviral compounds having a similarity score >0.6; were selected for further docking studies with wild and mutant NSPs and S Spike protein of SARS-CoV-2 variant B.1.617. The docking studies identified a potent analog MA-11, which exhibited the highest binding affinity towards wild and mutant proteins. Further, molecular dynamics simulation studies of selected compounds confirmed their perfect fitting into NSP12 and spike active sites and offer direction for further lead optimization and rational drug design.https://doi.org/10.2478/ebtj-2023-0009coronavirusescovid-19mutationnon-structural proteinssars-cov-2spike protein |
| spellingShingle | Madishetti Vinuthna Vani Reddy Sudhakar kalagara Sudhakar Garg Ashish Enaganti Sreenivas Hussain Sardar Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies The EuroBiotech Journal coronaviruses covid-19 mutation non-structural proteins sars-cov-2 spike protein |
| title | Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies |
| title_full | Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies |
| title_fullStr | Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies |
| title_full_unstemmed | Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies |
| title_short | Insilico Screening for Identification of Hits against SARS-Cov-2 Variant of Concern B.1.617 and NSP12 Mutants by Molecular Docking and Simulation Studies |
| title_sort | insilico screening for identification of hits against sars cov 2 variant of concern b 1 617 and nsp12 mutants by molecular docking and simulation studies |
| topic | coronaviruses covid-19 mutation non-structural proteins sars-cov-2 spike protein |
| url | https://doi.org/10.2478/ebtj-2023-0009 |
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