Developing Small-Molecule Inhibitors of Protein-Protein Interactions Involved in Viral Entry as Potential Antivirals for COVID-19

Buchwald, Péter

doi:10.3389/fddsv.2022.898035

Cited by 9 publications

(2 citation statements)

References 177 publications

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“…In conclusion, the results of this study have provided potential candidates for further development of therapeutics against SARS-CoV-2 infection. However, we also hope that the presented rapid, cost-effective peptide-based strategy for developing and optimizing efficient protein-protein interaction disruptors may be successfully applied to discover antiviral candidates against future emerging human viral infections ( Buchwald, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

Odolczyk

Klim²,

Podsiadła-Białoskórska³

et al. 2022

Front. Mol. Biosci.

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New pathogens responsible for novel human disease outbreaks in the last two decades are mainly the respiratory system viruses. Not different was the last pandemic episode, caused by infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One of the extensively explored targets, in the recent scientific literature, as a possible way for rapid development of COVID-19 specific drug(s) is the interaction between the receptor-binding domain of the virus’ spike (S) glycoprotein and human receptor angiotensin-converting enzyme 2 (hACE2). This protein-protein recognition process is involved in the early stages of the SARS-CoV-2 life cycle leading to the host cell membrane penetration. Thus, disrupting this interaction may block or significantly reduce the infection caused by the novel pathogen. Previously we have designed (by in silico structure-based analysis) three very short peptides having sequences inspirited by hACE2 native fragments, which effectively bind to the SARS-CoV-2 S protein and block its interaction with the human receptor. In continuation of the above mentioned studies, here we presented an application of molecular modeling approach resulting in improved binding affinity of the previously proposed ligand and its enhanced ability to inhibit meaningful host-virus protein-protein interaction. The new optimized hexapeptide binds to the virus protein with affinity one magnitude higher than the initial ligand and, as a very short peptide, has also great potential for further drug development. The peptide-based strategy is rapid and cost-effective for developing and optimizing efficient protein-protein interactions disruptors and may be successfully applied to discover antiviral candidates against other future emerging human viral infections.

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Section: Discussionmentioning

confidence: 99%

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

Odolczyk

Klim²,

Podsiadła-Białoskórska³

et al. 2022

Front. Mol. Biosci.

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“…These strategies aim to disrupt essential viral-host RBP interactions critical for viral replication and pathogenesis, providing novel avenues for therapeutic intervention. One approach involves the development of small molecule inhibitors that specifically target viral proteins interacting with host RBPs [31]. These inhibitors disrupt the protein-protein interactions necessary for viral replication and spread.…”

Section: Host Rbps Involved In Viral Pathogenesismentioning

confidence: 99%

Viral Hijacking of Host RNA-binding Proteins: Implications for Viral Replication and Pathogenesis

Serge Andigema

2024

JCLR

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In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis. Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections. Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy. As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combating viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\ Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

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Ethanol Inhalation as a Method to Denature the Spike Protein of SARS-CoV-2

Manning,

Livingston,

Persaud

et al. 2024

Advances in Experimental Medicine and Biology

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Developing Small-Molecule Inhibitors of Protein-Protein Interactions Involved in Viral Entry as Potential Antivirals for COVID-19

Cited by 9 publications

References 177 publications

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

Improvement of native structure-based peptides as efficient inhibitors of protein-protein interactions of SARS-CoV-2 spike protein and human ACE2

Viral Hijacking of Host RNA-binding Proteins: Implications for Viral Replication and Pathogenesis

Ethanol Inhalation as a Method to Denature the Spike Protein of SARS-CoV-2

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