Пожалуйста, используйте этот идентификатор, чтобы цитировать или ссылаться на этот ресурс:
http://elar.urfu.ru/handle/10995/118366
Название: | Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations |
Авторы: | Singh, R. Bhardwaj, V. K. Das, P. Bhattacherjee, D. Zyryanov, G. V. Purohit, R. |
Дата публикации: | 2022 |
Библиографическое описание: | Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations / R. Singh, V. K. Bhardwaj, P. Das et al. // Computers in Biology and Medicine. — 2022. — Vol. 146. — 105572. |
Аннотация: | Background: The SARS-CoV-2 main protease (Mpro) is an attractive target in the COVID-19 drug development process. It catalyzes the polyprotein's translation from viral RNA and specifies a particular cleavage site. Due to the absence of identical cleavage specificity in human cell proteases, targeting Mpro with chemical compounds can obstruct the replication of the virus. Methods: To explore the potential binding mechanisms of 1,2,3-triazole scaffolds in comparison to co-crystallized inhibitors 11a and 11b towards Mpro, we herein utilized molecular dynamics and enhanced sampling simulation studies. Results and conclusion: All the 1,2,3-triazole scaffolds interacted with catalytic residues (Cys145 and His41) and binding pocket residues of Mpro involving Met165, Glu166, Ser144, Gln189, His163, and Met49. Furthermore, the adequate binding free energy and potential mean force of the topmost compound 3h was comparable to the experimental inhibitors 11a and 11b of Mpro. Overall, the current analysis could be beneficial in developing the SARS-CoV-2 Mpro potential inhibitors. © 2022 Elsevier Ltd |
Ключевые слова: | 1,2,3-TRIAZOLE FREE ENERGY LANDSCAPE MD SIMULATION MM-PBSA UMBRELLA SAMPLING SIMULATION BINDING ENERGY DISEASES FREE ENERGY MOLECULAR DYNAMICS 1,2,3-TRIAZOLE DEVELOPMENT PROCESS DRUG DEVELOPMENT FREE ENERGY LANDSCAPE MD SIMULATION MM-PBSA SAMPLING SIMULATION STEERED MOLECULAR DYNAMICS SIMULATIONS UMBRELLA SAMPLING UMBRELLA SAMPLING SIMULATION SARS 1,2,3 TRIAZOLE DERIVATIVE CORONAVIRUS 3C PROTEASE CORONAVIRUS PROTEINASE INHIBITOR 3C-LIKE PROTEINASE, SARS-COV-2 CYSTEINE PROTEINASE PROTEINASE INHIBITOR TRIAZOLE DERIVATIVE VIRAL PROTEIN ARTICLE BINDING AFFINITY CONTROLLED STUDY DRUG DESIGN DRUG PROTEIN BINDING DRUG STABILITY ENZYME INHIBITION HYDROGEN BOND MOLECULAR DOCKING MOLECULAR DYNAMICS NONHUMAN SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 BENCHMARKING CHEMISTRY DRUG THERAPY HUMAN BENCHMARKING CORONAVIRUS 3C PROTEASES COVID-19 CYSTEINE ENDOPEPTIDASES HUMANS MOLECULAR DOCKING SIMULATION MOLECULAR DYNAMICS SIMULATION PROTEASE INHIBITORS SARS-COV-2 TRIAZOLES VIRAL NONSTRUCTURAL PROTEINS |
URI: | http://elar.urfu.ru/handle/10995/118366 |
Условия доступа: | info:eu-repo/semantics/openAccess |
Идентификатор SCOPUS: | 85129703595 |
Идентификатор WOS: | 000804709400004 |
Идентификатор PURE: | 30208707 |
DOI: | 10.1016/j.compbiomed.2022.105572 |
Сведения о поддержке: | 5058; Department of Biotechnology, Ministry of Science and Technology, India, DBT; Indian Council of Medical Research, ICMR; Council of Scientific and Industrial Research, India, CSIR; Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2020-777 We gratefully acknowledge to the Director, CSIR-Institute of Himalayan Bioresource Technology, Palampur for providing the facilities to carry out this work. This research received no specific grant from any funding agency. The work was carried out under the aegis of the Himalayan Centre for High-throughput Computational Biology (HiCHiCoB), a BIC supported by DBT. The CSIR support in the form of projects MLP:0201 and OLP:0043 for bioinformatics studies is highly acknowledged. R. S. expresses gratitude to the Indian Council of Medical Research, New Delhi, India for providing Senior Research Fellowship. G.V.Z. acknowledge the Ministry of Science and Higher Education of the Russian Federation within the framework of the grant agreement as government subsidies from the Federal budget in accordance with paragraph 4 of article 78.1 of the Budget Code of the Russian Federation (Moscow, October 1, 2020, No. 075-15-2020-777). This manuscript represents CSIR-IHBT communication no. 5058. We gratefully acknowledge to the Director, CSIR-Institute of Himalayan Bioresource Technology, Palampur for providing the facilities to carry out this work. This research received no specific grant from any funding agency. The work was carried out under the aegis of the Himalayan Centre for High-throughput Computational Biology (HiCHiCoB), a BIC supported by DBT. The CSIR support in the form of projects MLP:0201 and OLP:0043 for bioinformatics studies is highly acknowledged. R. S. expresses gratitude to the Indian Council of Medical Research, New Delhi, India for providing Senior Research Fellowship. G.V.Z. acknowledge the Ministry of Science and Higher Education of the Russian Federation within the framework of the grant agreement as government subsidies from the Federal budget in accordance with paragraph 4 of article 78.1 of the Budget Code of the Russian Federation (Moscow, October 1, 2020, No. 075-15-2020-777). This manuscript represents CSIR-IHBT communication no. 5058. |
Располагается в коллекциях: | Научные публикации, проиндексированные в SCOPUS и WoS CC |
Файлы этого ресурса:
Файл | Описание | Размер | Формат | |
---|---|---|---|---|
2-s2.0-85129703595.pdf | 8,37 MB | Adobe PDF | Просмотреть/Открыть |
Все ресурсы в архиве электронных ресурсов защищены авторским правом, все права сохранены.