دورية أكاديمية
Investigation of protein-protein interactions and hotspot region on the NSP7-NSP8 binding site in NSP12 of SARS-CoV-2.
| العنوان: | Investigation of protein-protein interactions and hotspot region on the NSP7-NSP8 binding site in NSP12 of SARS-CoV-2. |
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| المؤلفون: | Lima Neto JX; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil., Bezerra KS; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil., Barbosa ED; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil., Araujo RL; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil., Galvão DS; Applied Physics Department, University of Campinas, Campinas, São Paulo, Brazil., Lyra ML; Physics Institute, Federal University of Alagoas, Maceió, Brazil., Oliveira JIN; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil., Akash S; Department of Pharmacy, Daffodil International University, Dhaka, Bangladesh., Jardan YAB; Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Nafidi HA; Department of Food Science, Faculty of Agricultural and Food Sciences, Laval University, Quebec City, QC, Canada., Bourhia M; Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco., Fulco UL; Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, Brazil. |
| المصدر: | Frontiers in molecular biosciences [Front Mol Biosci] 2024 Jan 18; Vol. 10, pp. 1325588. Date of Electronic Publication: 2024 Jan 18 (Print Publication: 2023). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101653173 Publication Model: eCollection Cited Medium: Print ISSN: 2296-889X (Print) Linking ISSN: 2296889X NLM ISO Abbreviation: Front Mol Biosci Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media S.A., [2014]- |
| مستخلص: | Background: The RNA-dependent RNA polymerase (RdRp) complex, essential in viral transcription and replication, is a key target for antiviral therapeutics. The core unit of RdRp comprises the nonstructural protein NSP12, with NSP7 and two copies of NSP8 (NSP81 and NSP82) binding to NSP12 to enhance its affinity for viral RNA and polymerase activity. Notably, the interfaces between these subunits are highly conserved, simplifying the design of molecules that can disrupt their interaction. Methods: We conducted a detailed quantum biochemical analysis to characterize the interactions within the NSP12-NSP7, NSP12-NSP81, and NSP12-NSP82 dimers. Our objective was to ascertain the contribution of individual amino acids to these protein-protein interactions, pinpointing hotspot regions crucial for complex stability. Results: The analysis revealed that the NSP12-NSP81 complex possessed the highest total interaction energy (TIE), with 14 pairs of residues demonstrating significant energetic contributions. In contrast, the NSP12-NSP7 complex exhibited substantial interactions in 8 residue pairs, while the NSP12-NSP82 complex had only one pair showing notable interaction. The study highlighted the importance of hydrogen bonds and π-alkyl interactions in maintaining these complexes. Intriguingly, introducing the RNA sequence with Remdesivir into the complex resulted in negligible alterations in both interaction energy and geometric configuration. Conclusion: Our comprehensive analysis of the RdRp complex at the protein-protein interface provides invaluable insights into interaction dynamics and energetics. These findings can guide the design of small molecules or peptide/peptidomimetic ligands to disrupt these critical interactions, offering a strategic pathway for developing effective antiviral drugs. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Lima Neto, Bezerra, Barbosa, Araujo, Galvão, Lyra, Oliveira, Akash, Jardan, Nafidi, Bourhia and Fulco.) |
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| فهرسة مساهمة: | Keywords: NSP7-NSP8 binding site; SARS CoV-2; and infectious disease; computational biology; drug design |
| تواريخ الأحداث: | Date Created: 20240202 Latest Revision: 20240203 |
| رمز التحديث: | 20240205 |
| مُعرف محوري في PubMed: | PMC10830813 |
| DOI: | 10.3389/fmolb.2023.1325588 |
| PMID: | 38304231 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2296-889X |
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| DOI: | 10.3389/fmolb.2023.1325588 |