Evaluating the potential of different inhibitors on RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 : A molecular modeling approach
© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd..
BACKGROUND: Coronavirus disease 2019 (COVID-19) has already affected 2883603 and killed 198842 people, as of April 27, 2020. Because there is no specific therapeutic drug, drug repurposing has been proposed. RNA-dependent RNA polymerase (RdRp) is a promising drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control its replication, and several compounds have been suggested. The present study predicts relative efficacies of thirty known or repurposed compounds in inhibiting the RdRp.
METHODS: The three-dimensional structure of the target enzyme was loaded into Molegro virtual docker software, followed by chemical structures of the test compounds. The docking was performed between the compounds and the active site of the enzyme to determine docking scores, and the energy liberated when the two dock. Thus, docking scores signify the affinity of ligand(s) with the active site of enzyme(s) and thus its inhibitory potential.
RESULTS: Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp. Among all compounds, chlorhexidine was predicted as the most potent inhibitor. Furthermore, the results predict the relative efficacy of different drugs as inhibitors of the drug target.
CONCLUSION: While the study identifies several compounds as inhibitors of RdRp of SARS-CoV-2, the prediction of their relative efficacies may be useful in future studies. While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site. Thus, based on the findings, we recommend in vitro and in vivo studies and clinical trials to determine their effectiveness against COVID-19.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:77 |
|---|---|
| Enthalten in: |
Medical journal, Armed Forces India - 77(2021) vom: 18. Juli, Seite S373-S378 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Choudhury, Shuvasish [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2019-nCoV |
|---|
| Anmerkungen: |
Date Revised 25.04.2022 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1016/j.mjafi.2020.05.005 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM314101489 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM314101489 | ||
| 003 | DE-627 | ||
| 005 | 20231225152014.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.mjafi.2020.05.005 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1046.xml |
| 035 | |a (DE-627)NLM314101489 | ||
| 035 | |a (NLM)32836709 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Choudhury, Shuvasish |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evaluating the potential of different inhibitors on RNA-dependent RNA polymerase of severe acute respiratory syndrome coronavirus 2 |b A molecular modeling approach |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 25.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd. | ||
| 520 | |a BACKGROUND: Coronavirus disease 2019 (COVID-19) has already affected 2883603 and killed 198842 people, as of April 27, 2020. Because there is no specific therapeutic drug, drug repurposing has been proposed. RNA-dependent RNA polymerase (RdRp) is a promising drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to control its replication, and several compounds have been suggested. The present study predicts relative efficacies of thirty known or repurposed compounds in inhibiting the RdRp | ||
| 520 | |a METHODS: The three-dimensional structure of the target enzyme was loaded into Molegro virtual docker software, followed by chemical structures of the test compounds. The docking was performed between the compounds and the active site of the enzyme to determine docking scores, and the energy liberated when the two dock. Thus, docking scores signify the affinity of ligand(s) with the active site of enzyme(s) and thus its inhibitory potential | ||
| 520 | |a RESULTS: Among known inhibitors, remdesivir was found to have the highest affinity for the active site of the RdRp. Among all compounds, chlorhexidine was predicted as the most potent inhibitor. Furthermore, the results predict the relative efficacy of different drugs as inhibitors of the drug target | ||
| 520 | |a CONCLUSION: While the study identifies several compounds as inhibitors of RdRp of SARS-CoV-2, the prediction of their relative efficacies may be useful in future studies. While nucleoside analogs compete with the natural substrate of RdRp, thereby terminating RNA replication, other compounds would physically block entry of the natural substrates into the active site. Thus, based on the findings, we recommend in vitro and in vivo studies and clinical trials to determine their effectiveness against COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 2019-nCoV | |
| 650 | 4 | |a Betacoronavirus | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Molecular docking | |
| 650 | 4 | |a Pneumonia | |
| 700 | 1 | |a Moulick, Debojyoti |e verfasserin |4 aut | |
| 700 | 1 | |a Saikia, Purbajyoti |e verfasserin |4 aut | |
| 700 | 1 | |a Mazumder, Muhammed Khairujjaman |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Medical journal, Armed Forces India |d 1994 |g 77(2021) vom: 18. Juli, Seite S373-S378 |w (DE-627)NLM075786907 |x 0377-1237 |7 nnns |
| 773 | 1 | 8 | |g volume:77 |g year:2021 |g day:18 |g month:07 |g pages:S373-S378 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.mjafi.2020.05.005 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 77 |j 2021 |b 18 |c 07 |h S373-S378 | ||