SARS-COV-2 Coronavirus Papain-like Protease PLpro as an Antiviral Target for Inhibitors of Active Site and Protein–Protein Interactions

Ершов, П. В.; Yablokov, E. O.; Mezentsev, Yu. V.; Chuev, G. N.; Fedotova, M. V.; Kruchinin, Sergey E.; Иванов, А. С.

doi:10.1134/s0006350922060082

Cited by 4 publications

(2 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PL pro is a monomeric enzyme characterized by four subdomains: the N-terminal ubiquitin-like domain (Ubl), the α-helical thumb domain, the β-stranded finger domain, and the palm domain. The catalytic triad responsible for PL pro 's enzymatic activity includes Cys111, His272, Tyr264, Tyr268, and Asp286 [53,56,67,68]. PL pro is highly similar to its counterpart in the SARS-CoV virus, sharing conserved structural features and an impressive 82% sequence identity.…”

Section: Molecular Docking Analysismentioning

confidence: 99%

See 1 more Smart Citation

Deciphering the Molecular Interaction Process of Gallium Maltolate on SARS-CoV-2 Main and Papain-Like Proteases: A Theoretical Study

Taype-Huanca,

Osorio,

Inostroza

et al. 2024

Biophysica

View full text Add to dashboard Cite

This study explored the inhibitory potential of gallium maltolate against severe acute respiratory syndrome coronavirus 2 and main and papain-like proteases. Computational methods, including density functional theory and molecular docking, were used to assess gallium maltolate reactivity and binding interactions. Density functional theory calculations revealed gallium maltolate’s high electron-capturing capacity, particularly around the gallium metal atom, which may contribute to their activity. Molecular docking demonstrated that gallium maltolate can form strong hydrogen bonds with key amino acid residues like glutamate-166 and cysteine-145, tightly binding to main and papain-like proteases. The binding energy and interactions of gallium maltolate were comparable to known SARS-CoV-2 inhibitors like N-[(5-methyl-1,2-oxazol-3-yl)carbonyl]-L-alanyl-L-valyl-N-{(2S,3E)-5-(benzyloxy)-5-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]pent-3-en-2-yl}-L-leucinamide, indicating its potential as an antiviral agent. However, further experimental validation is required to confirm its effectiveness in inhibiting SARS-CoV-2 replication and treating COVID-19.

show abstract

Section: Molecular Docking Analysismentioning

confidence: 99%

“…The S3-S4 subsites within the substrate binding cleft are critical for accommodating key inhibitor groups, such as the zinc-binding moiety of TTT. Inhibitors targeting cysteine residues in the zinc-binding domain are particularly promising for drug development [53,56,67].…”

Section: Molecular Docking Analysismentioning

confidence: 99%