Version 1
: Received: 25 November 2023 / Approved: 27 November 2023 / Online: 27 November 2023 (16:52:17 CET)
Version 2
: Received: 27 December 2023 / Approved: 28 December 2023 / Online: 28 December 2023 (13:51:47 CET)
Version 3
: Received: 23 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (13:51:28 CET)
How to cite:
Mohammed, M.; Chougule, K.S.; Ala, C.; Kuthe, P.V.; Garg, M.; Sankaranarayanan, M.; Vasan, S.S. In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC. Preprints2023, 2023111727. https://doi.org/10.20944/preprints202311.1727.v2
Mohammed, M.; Chougule, K.S.; Ala, C.; Kuthe, P.V.; Garg, M.; Sankaranarayanan, M.; Vasan, S.S. In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC. Preprints 2023, 2023111727. https://doi.org/10.20944/preprints202311.1727.v2
Mohammed, M.; Chougule, K.S.; Ala, C.; Kuthe, P.V.; Garg, M.; Sankaranarayanan, M.; Vasan, S.S. In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC. Preprints2023, 2023111727. https://doi.org/10.20944/preprints202311.1727.v2
APA Style
Mohammed, M., Chougule, K.S., Ala, C., Kuthe, P.V., Garg, M., Sankaranarayanan, M., & Vasan, S.S. (2023). In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC. Preprints. https://doi.org/10.20944/preprints202311.1727.v2
Chicago/Turabian Style
Mohammed, M., Murugesan Sankaranarayanan and Seshadri S Vasan. 2023 "In Silico Exploration of Bisphosphonate Scaffolds as Potential Inhibitors of SARS-CoV-2 RdRp for COVID-19 and PASC" Preprints. https://doi.org/10.20944/preprints202311.1727.v2
Abstract
The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this paper. We have investigated bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates for further evaluation (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211). Interestingly, one of these (CHEMBL608526) very closely resembles the approved drug minodronate, and another (CHEMBL98211) resembles the approved drug zoledronate.
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
28 December 2023
Commenter:
Seshadri Vasan
Commenter's Conflict of Interests:
Author
Comment:
Revised version addressing feedback from the editor and three peer-reviewers. Main difference is inclusion of protomers leading to seven hit candidates, including two resembling minodronate and zoledronate.
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Commenter: Seshadri Vasan
Commenter's Conflict of Interests: Author