<i>In silico</i> design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein

Wu, Jianhua; Zhang, Hongxing; Zhang, Ji-Long

doi:10.1039/d3cp01167d

Search citation statements

Order By: Relevance

Paper Sections

Select...

Identification Of Key Residues and Interaction Analysis1

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2023

2024

Publication Types

Select...

Article2

Relationship

Self Cite1

Independent1

Authors

Journals

Cited by 2 publications

(1 citation statement)

References 61 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6B. 55 The catalytic pocket of 3CLpro protein encompasses four sites: S1 0 , S1, S2, and S4. The isoquinoline ring of the small molecule WU-04 is docked at the S1 site.…”

Section: Identification Of Key Residues and Interaction Analysismentioning

confidence: 99%

The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses

Wu,

Zhang,

Zhang

2023

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

show abstract

“…6B. 55 The catalytic pocket of 3CLpro protein encompasses four sites: S1 0 , S1, S2, and S4. The isoquinoline ring of the small molecule WU-04 is docked at the S1 site.…”

Section: Identification Of Key Residues and Interaction Analysismentioning

confidence: 99%

The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses

Wu,

Zhang,

Zhang

2023

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

show abstract

Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant

An,

Yang,

Luo

et al. 2024

Proteins

View full text Add to dashboard Cite

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) characterized by 30 mutations in its spike protein, has rapidly spread worldwide since November 2021, significantly exacerbating the ongoing COVID‐19 pandemic. In order to investigate the relationship between these mutations and the variant's high transmissibility, we conducted a systematic analysis of the mutational effect on spike–angiotensin‐converting enzyme‐2 (ACE2) interactions and explored the structural/energy correlation of key mutations, utilizing a reliable coarse‐grained model. Our study extended beyond the receptor‐binding domain (RBD) of spike trimer through comprehensive modeling of the full‐length spike trimer rather than just the RBD. Our free‐energy calculation revealed that the enhanced binding affinity between the spike protein and the ACE2 receptor is correlated with the increased structural stability of the isolated spike protein, thus explaining the omicron variant's heightened transmissibility. The conclusion was supported by our experimental analyses involving the expression and purification of the full‐length spike trimer. Furthermore, the energy decomposition analysis established those electrostatic interactions make major contributions to this effect. We categorized the mutations into four groups and established an analytical framework that can be employed in studying future mutations. Additionally, our calculations rationalized the reduced affinity of the omicron variant towards most available therapeutic neutralizing antibodies, when compared with the wild type. By providing concrete experimental data and offering a solid explanation, this study contributes to a better understanding of the relationship between theories and observations and lays the foundation for future investigations.

show abstract

In silico design of miniprotein to inhibit SARS-CoV-2 variant Omicron spike protein

Abstract: Both single- and double-point mutant inhibitors M7E, M7E + M43W, and M7E + M43Y based on the initial inhibitor AHB2 expressed enhanced inhibitory ability against the SARS-CoV-2 variant of Omicron RBD protein.

Cited by 2 publications

References 61 publications

The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses

The molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses

Mechanistic study of the transmission pattern of the SARS‐CoV‐2 omicron variant

Contact Info

Product

Resources

About