Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies
In this article, 34 anticoagulant drugs were screened in silico against the main protease (M<sup>pro</sup>) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 M<su...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12235 |
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| author | Ayman Abo Elmaaty Wagdy M. Eldehna Muhammad Khattab Omnia Kutkat Radwan Alnajjar Ahmed N. El-Taweel Sara T. Al-Rashood Mohammed A. S. Abourehab Faizah A. Binjubair Mohamed A. Saleh Amany Belal Ahmed A. Al-Karmalawy |
| author_facet | Ayman Abo Elmaaty Wagdy M. Eldehna Muhammad Khattab Omnia Kutkat Radwan Alnajjar Ahmed N. El-Taweel Sara T. Al-Rashood Mohammed A. S. Abourehab Faizah A. Binjubair Mohamed A. Saleh Amany Belal Ahmed A. Al-Karmalawy |
| author_sort | Ayman Abo Elmaaty |
| collection | DOAJ |
| description | In this article, 34 anticoagulant drugs were screened in silico against the main protease (M<sup>pro</sup>) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 M<sup>pro</sup>. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC<sub>50</sub>). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC<sub>50</sub> value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC<sub>50</sub> values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 M<sup>pro</sup> enzyme was investigated by utilizing the SARS-CoV-2 M<sup>pro</sup> assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 M<sup>pro</sup> inhibitory potential was attained for fondaparinux sodium with an IC<sub>50</sub> value of 2.36 µM, surpassing the reference tipranavir (IC<sub>50</sub> = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 M<sup>pro</sup> inhibitory potential was attained for dabigatran with an IC<sub>50</sub> value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches. |
| first_indexed | 2024-03-09T20:07:08Z |
| format | Article |
| id | doaj.art-cd3ff790d35947889a9d79283f57259f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:07:08Z |
| publishDate | 2022-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cd3ff790d35947889a9d79283f57259f2023-11-24T00:29:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201223510.3390/ijms232012235Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR StudiesAyman Abo Elmaaty0Wagdy M. Eldehna1Muhammad Khattab2Omnia Kutkat3Radwan Alnajjar4Ahmed N. El-Taweel5Sara T. Al-Rashood6Mohammed A. S. Abourehab7Faizah A. Binjubair8Mohamed A. Saleh9Amany Belal10Ahmed A. Al-Karmalawy11Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University, Port Said 42526, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, EgyptDepartment of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Institute, National Research Centre, El-Buhouth St., Dokki, Cairo 12622, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, EgyptDepartment of Chemistry, Faculty of Science, University of Benghazi, Benghazi 16063, LibyaCenter of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, EgyptDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesMedicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, EgyptPharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza 12566, EgyptIn this article, 34 anticoagulant drugs were screened in silico against the main protease (M<sup>pro</sup>) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 M<sup>pro</sup>. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC<sub>50</sub>). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC<sub>50</sub> value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC<sub>50</sub> values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 M<sup>pro</sup> enzyme was investigated by utilizing the SARS-CoV-2 M<sup>pro</sup> assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 M<sup>pro</sup> inhibitory potential was attained for fondaparinux sodium with an IC<sub>50</sub> value of 2.36 µM, surpassing the reference tipranavir (IC<sub>50</sub> = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 M<sup>pro</sup> inhibitory potential was attained for dabigatran with an IC<sub>50</sub> value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.https://www.mdpi.com/1422-0067/23/20/12235SARS-CoV-2M<sup>pro</sup>anticoagulantsin vitroin silico |
| spellingShingle | Ayman Abo Elmaaty Wagdy M. Eldehna Muhammad Khattab Omnia Kutkat Radwan Alnajjar Ahmed N. El-Taweel Sara T. Al-Rashood Mohammed A. S. Abourehab Faizah A. Binjubair Mohamed A. Saleh Amany Belal Ahmed A. Al-Karmalawy Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies International Journal of Molecular Sciences SARS-CoV-2 M<sup>pro</sup> anticoagulants in vitro in silico |
| title | Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies |
| title_full | Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies |
| title_fullStr | Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies |
| title_full_unstemmed | Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies |
| title_short | Anticoagulants as Potential SARS-CoV-2 M<sup>pro</sup> Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies |
| title_sort | anticoagulants as potential sars cov 2 m sup pro sup inhibitors for covid 19 patients in vitro molecular docking molecular dynamics dft and sar studies |
| topic | SARS-CoV-2 M<sup>pro</sup> anticoagulants in vitro in silico |
| url | https://www.mdpi.com/1422-0067/23/20/12235 |
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