Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics : Insights for developing potent drugs targeting SARS-CoV-2 and other viruses
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: The global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain.
METHODS: Integrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB.
RESULTS: We analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug.
CONCLUSIONS: The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Journal of infection and public health - 16(2023), 7 vom: 21. Juli, Seite 1048-1056 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chakraborty, Chiranjib [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
63231-63-0 |
|---|
| Anmerkungen: |
Date Completed 05.06.2023 Date Revised 05.06.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jiph.2023.05.010 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356989356 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356989356 | ||
| 003 | DE-627 | ||
| 005 | 20231226071625.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jiph.2023.05.010 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1189.xml |
| 035 | |a (DE-627)NLM356989356 | ||
| 035 | |a (NLM)37196368 | ||
| 035 | |a (PII)S1876-0341(23)00166-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chakraborty, Chiranjib |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics |b Insights for developing potent drugs targeting SARS-CoV-2 and other viruses |
| 264 | 1 | |c 2023 | |
| 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 Completed 05.06.2023 | ||
| 500 | |a Date Revised 05.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: The global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain | ||
| 520 | |a METHODS: Integrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB | ||
| 520 | |a RESULTS: We analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug | ||
| 520 | |a CONCLUSIONS: The results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7-nsp8-nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Favipiravir-RTP | |
| 650 | 4 | |a RdRp complex | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a Structural and molecular interaction | |
| 650 | 7 | |a favipiravir |2 NLM | |
| 650 | 7 | |a EW5GL2X7E0 |2 NLM | |
| 650 | 7 | |a RNA-Dependent RNA Polymerase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.48 |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Bhattacharya, Manojit |e verfasserin |4 aut | |
| 700 | 1 | |a Saha, Abinit |e verfasserin |4 aut | |
| 700 | 1 | |a Alshammari, Abdulrahman |e verfasserin |4 aut | |
| 700 | 1 | |a Alharbi, Metab |e verfasserin |4 aut | |
| 700 | 1 | |a Saikumar, G |e verfasserin |4 aut | |
| 700 | 1 | |a Pal, Soumen |e verfasserin |4 aut | |
| 700 | 1 | |a Dhama, Kuldeep |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sang-Soo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of infection and public health |d 2008 |g 16(2023), 7 vom: 21. Juli, Seite 1048-1056 |w (DE-627)NLM200240730 |x 1876-035X |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2023 |g number:7 |g day:21 |g month:07 |g pages:1048-1056 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jiph.2023.05.010 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2023 |e 7 |b 21 |c 07 |h 1048-1056 | ||