Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes

Bhardwaj, Taniya; Gadhave, Kundlik; Kapuganti, Shivani Krishna; Kumar, Prateek; Brotzakis, Z. Faidon; Saumya, Kumar Udit; Nayak, Namyashree; Kumar, Ankur; Joshi, Richa; Mukherjee, Bodhidipra; Bhardwaj, Aparna; Thakur, Krishan Gopal; Garg, Neha; Vendruscolo, Michele; Giri, Rajanish

doi:10.1038/s41467-023-36234-4

Cited by 24 publications

(16 citation statements)

References 69 publications

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“…New findings point to a delicate communication between the viral and host proteomes after infection, including the cross-seeding of host proteins by viral proteins [ 19 , 78 , 79 , 80 , 81 , 82 , 83 , 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

et al. 2023

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For a long time, studies of amyloidogenic proteins and peptides (amyloidogenic PPs) have been focused basically on their harmful properties and association with diseases. A vast amount of research has investigated the structure of pathogenic amyloids forming fibrous deposits within or around cells and the mechanisms of their detrimental actions. Much less has been known about the physiologic functions and beneficial properties of amyloidogenic PPs. At the same time, amyloidogenic PPs have various useful properties. For example, they may render neurons resistant to viral infection and propagation and stimulate autophagy. We discuss here some of amyloidogenic PPs’ detrimental and beneficial properties using as examples beta-amyloid (β-amyloid), implicated in the pathogenesis of Alzheimer’s disease (AD), and α-synuclein—one of the hallmarks of Parkinson’s disease (PD). Recently amyloidogenic PPs’ antiviral and antimicrobial properties have attracted attention because of the COVID-19 pandemic and the growing threat of other viral and bacterial-induced diseases. Importantly, several COVID-19 viral proteins, e.g., spike, nucleocapsid, and envelope proteins, may become amyloidogenic after infection and combine their harmful action with the effect of endogenous APPs. A central area of current investigations is the study of the structural properties of amyloidogenic PPs, defining their beneficial and harmful properties, and identifying triggers that transform physiologically important amyloidogenic PPs into vicious substances. These directions are of paramount importance during the current SARS-CoV-2 global health crisis.

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Section: Discussionmentioning

confidence: 99%

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

et al. 2023

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“…Evidence shows that viruses have been evolving to be more pathogenic, and their proteins are adopting misfolded conformations while also affecting the host protein‐folding pathways. They can exert their pathogenesis through an aggregation‐mediated pathway where the viral proteins cannot only form insoluble aggregates but also form hetero‐oligomeric fibrils with host proteins (Bhardwaj et al, 2023; Chevalier et al, 2010; Pham et al, 2019). PB1‐F2 protein of influenza itself adopts β‐sheets conformation and forms amorphous aggregates in vitro (Chevalier et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it interacts with host proteins such as RIPK1 and RIPK3 and forms hetero-oligomeric amyloid fibrils altering their natural functions (Pham et al, 2019). Recently, many protein regions of SARS coronaviruses also have been observed to form insoluble amyloid structures in vitro (Bhardwaj et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Widespread amyloid aggregates formation by Zika virus proteins and peptides

Giri,

Bhardwaj,

Kapuganti

et al. 2023

Protein Science

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Viral pathogenesis typically involves numerous molecular mechanisms. Protein aggregation is a relatively unknown characteristic of viruses, despite the fact that viral proteins have been shown to form terminally misfolded forms. Zika virus (ZIKV) is a neurotropic one with the potential to cause neurodegeneration. Its protein amyloid aggregation may link the neurodegenerative component to the pathogenicity associated with the viral infection. Therefore, we investigated protein aggregation in the ZIKV proteome as a putative pathogenic route and one of the alternate pathways. We discovered that it contains numerous anticipated aggregation‐prone regions in this investigation. To validate our prediction, we used a combination of supporting experimental techniques routinely used for morphological characterization and study of amyloid aggregates. Several ZIKV proteins and peptides, including the full‐length envelope protein, its domain III (EDIII) and fusion peptide, Pr N‐terminal peptide, NS1 β‐roll peptide, membrane‐embedded signal peptide 2K, and cytosolic region of NS4B protein, were shown to be highly aggregating in our study. Because our findings show that viral proteins can form amyloids in vitro, we need to do a thorough functional study of these anticipated APRs to understand better the role of amyloids in the pathophysiology of ZIKV infection.

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“…Additionally, Schiff bases derived from 2-thiophene carboxaldehyde find diverse applications, ranging from serving as photosensitizing catalysts 40,41 to contributing to optical materials 42,43 and the production of anticorrosive materials. 44,45 Notably, tellurium metal complexes 46,47 have gained significance due to their relevance in biological processes. The antimicrobial behavior exhibited by tellurium complexes is attributed to chelation, which results in a reduction in the polarity of tellurium metal.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the biomedical potential of thiophene‐derived Schiff base complexes: A comprehensive study of synthesis, spectral characterization, antimicrobial efficacy, antioxidant activity, and computational insights

Bhardwaj,

Dubey,

Tufail

et al. 2024

Applied Organom Chemis

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In our pursuit of designing potent bioactive compounds, we synthesized six novel tellurium (IV) complexes through the condensation of 5‐methyl‐2‐thiophene carboxaldehyde and p‐nitroaniline. These compounds underwent rigorous investigation using various analytical techniques (TGA, SEM, EDAX, and powder XRD) and spectral analyses (NMR, mass spectrometry, UV–Vis, and FTIR). Spectroscopic analysis suggested an octahedral geometry for the complexes, revealing chelation through the thiophene sulfur and azomethine nitrogen atoms. Thermal analysis indicated a three‐step degradation process, ultimately leaving behind metal oxide as the end product. We conducted in‐vitro antimicrobial screening using the broth micro‐dilution method, highlighting the significant antimicrobial and antioxidant properties of complexes 3c and 3d, as well as the potent antimicrobial activity of 3b and 3f against various bacterial strains, including Candida albicans. To further substantiate our findings, we performed advanced computational analyses, including molecular docking, pharmacophore modeling, DFT, MESP, and ADMET studies. Molecular docking validated our antimicrobial results, whereas pharmacophore models enhanced our understanding of molecular interactions with proteins, potentially identifying novel bioactive compounds. Furthermore, DFT and MESP investigations underscored the superior biological efficacy of tellurium (IV) complexes over thiophene‐derived ligands, emphasizing their potential as therapeutic agents. ADMET analysis revealed their favorable profile as precursors for drug development with minimal adverse effects. In summary, our research seamlessly integrates experimental and theoretical aspects, offering innovative insights into drug design and potential applications in pharmaceuticals. This study represents a significant milestone, paving the way for future advancements in the field of pharmaceutical science.

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Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes

Cited by 24 publications

References 69 publications

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era

Widespread amyloid aggregates formation by Zika virus proteins and peptides

Unveiling the biomedical potential of thiophene‐derived Schiff base complexes: A comprehensive study of synthesis, spectral characterization, antimicrobial efficacy, antioxidant activity, and computational insights

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