Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332
Abstract
:1. Introduction
2. Materials and Methods
2.1. Expression and Purification of SARS-CoV-2 Mpro D48N Mutant
2.2. Enzymatic Inhibition Assays
2.3. Crystallization of Mpro D48N-Shikonin and Mpro D48N-FP07321332 Complexes
2.4. Data Collection, Structure Determination, and Refinement
3. Results
3.1. Structure Determination of Mpro D48N-PF-07321332 and Mpro D48N-Shikonin Complexes
3.2. Inhibitory Activities of PF-07321332 and Shikonin against SARS-CoV-2-Mpro D48N
3.3. Inhibitory Mechanism of Shikonin against SARS-CoV-2-Mpro D48N
3.4. Inhibitory Mechanism of PF-07321332 against SARS-CoV-2-D48N Mpro
3.5. Structural Comparison of Mpro D48N Mutant to Wild-Type Mpro When Bound to Shikonin and PF-07321332
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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SARS-CoV-2 Mpro D48N PF-07321332 | SARS-CoV-2 Mpro D48N-Shikonin | |
---|---|---|
PDB code | 7XB4 | 8WUR |
Data collection | ||
Synchrotron | SSRF | SSRF |
Beam line | BL02U1 | BL02U1 |
Wavelength (Å) | 0.97918 | 0.97918 |
Space group | P212121 | P212121 |
a, b, c (Å) | 68.15, 102.66, 103.36 | 68.05, 102.94, 103.69 |
α, β, γ (°) | 90.00, 90.00, 90.00 | 90.00, 90.00, 90.00 |
Total reflections | 436,396 | 543,759 |
Unique reflections | 42,254 | 44,801 |
Resolution (Å) | 2.07(2.07–2.20) | 2.08(2.08–2.19) |
R-merge (%) | 3.7(86.1) | 3.1(106.6) |
Mean I/σ (I) | 15.7/3.1 | 18.5/2.7 |
Completeness (%) | 94.4(99.9) | 100.0(100.0) |
Redundancy | 10.3(9.9) | 12.1(11.4) |
Refinement | ||
Resolution (Å) | 56.9–2.07 | 46.30–2.08 |
Rwork/Rfree (%) | 21.09/24.03 | 21.07/23.85 |
Atoms | 4514 | 4568 |
Mean temperature factor (Å2) | 36.3 | 43.5 |
Bond lengths (Å) | 0.008 | 0.008 |
Bond angles (°) | 0.934 | 0.969 |
Preferred | 97.28 | 96.90 |
Allowed | 2.72 | 3.10 |
outliers | 0 | 0 |
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Zhao, Z.; Zhu, Q.; Zhou, X.; Li, W.; Yin, X.; Li, J. Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332. Viruses 2024, 16, 65. https://doi.org/10.3390/v16010065
Zhao Z, Zhu Q, Zhou X, Li W, Yin X, Li J. Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332. Viruses. 2024; 16(1):65. https://doi.org/10.3390/v16010065
Chicago/Turabian StyleZhao, Zhenyu, Qinyao Zhu, Xuelan Zhou, Wenwen Li, Xiushan Yin, and Jian Li. 2024. "Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332" Viruses 16, no. 1: 65. https://doi.org/10.3390/v16010065
APA StyleZhao, Z., Zhu, Q., Zhou, X., Li, W., Yin, X., & Li, J. (2024). Structural Basis for the Inhibition of SARS-CoV-2 Mpro D48N Mutant by Shikonin and PF-07321332. Viruses, 16(1), 65. https://doi.org/10.3390/v16010065