Structural and Functional Aspects of Ebola Virus Proteins

Jain, Sahil; Martynova, Ekaterina; Rizvanov, Albert A.; Khaiboullina, Svetlana; Baranwal, Manoj

doi:10.3390/pathogens10101330

Cited by 44 publications

(74 citation statements)

References 212 publications

(328 reference statements)

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“…The genome of the Ebola virus encodes seven structural proteins, namely, NP, VP35, VP40, GP, VP30, VP24, and L [ 53 ]. VP40 is the most abundantly expressed EBOV protein, making it an attractive target for drug design [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

Bergasa-Caceres

Rabitz

2022

IJMS

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In a recent paper, we proposed the folding interdiction target region (FITR) strategy for therapeutic drug design in SARS-CoV-2. This paper expands the application of the FITR strategy by proposing therapeutic drug design approaches against Ebola virus disease and influenza A. We predict target regions for folding interdicting drugs on correspondingly relevant structural proteins of both pathogenic viruses: VP40 of Ebola, and matrix protein M1 of influenza A. Identification of the protein targets employs the sequential collapse model (SCM) for protein folding. It is explained that the model predicts natural peptide candidates in each case from which to start the search for therapeutic drugs. The paper also discusses how these predictions could be tested, as well as some challenges likely to be found when designing effective therapeutic drugs from the proposed peptide candidates. The FITR strategy opens a potential new avenue for the design of therapeutic drugs that promises to be effective against infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

Bergasa-Caceres

Rabitz

2022

IJMS

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“…Similarly, filovirus such as EBOV, inhibits IFN-response at different levels (86). First, EBOV VP35 circumvent innate sensing by RLRs due to its capacity to bind double-stranded RNA (dsRNA), blocking RIG-I and MDA-5 recognition.…”

Section: Ifn-based Therapiesmentioning

confidence: 99%

“…Indeed, VP35 has been shown to prevent PACT-induced RIG-I ATPase activity and RIG-I activation (87,88). Moreover, as alternative host-based intervention to be explored, VP35 also impairs TBK-1/IKKϵ interaction with IRF3, blocking IRF3 dimerization, phosphorylation and nuclear translocation (86). Other EBOV proteins also participate in the IFN-evasion mechanisms as for example VP24 which has been described to arrest nuclear transportation of tyrosine phosphorylated STAT1 through the interaction with cellular protein NPI-1 (86).…”

Section: Ifn-based Therapiesmentioning

confidence: 99%

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

Badía

García-Vidal²,

Ballana³

2022

Front. Virol.

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The development of antiviral drugs, has provided enormous achievements in our recent history in the fight against viral infections. To date, most of the approved antiviral drugs target virus-encoded proteins to achieve direct antiviral activity. Nonetheless, the inherent idiosyncrasy of viral mutations during their replication cycle, enable many viruses to adapt to the new barriers, becoming resistant to therapies, therefore, representing an ever-present menace and prompting the scientific community towards the development of novel therapeutic strategies. Taking advantage of the increasing knowledge of virus-host cell interactions, the targeting of cellular factors or pathways essential for virus survival turns into an alternative strategy to intervene in almost every step of viral replication cycle. Since host factors are evolutionary conserved, viral evasion to host-directed therapies (HDT) would impose a higher genetic barrier to the emergence of resistant strains. Thus, targeting host factors has long been considered an alternative strategy to overcome viral resistance. Nevertheless, targeting host factors or pathways potentially hints undesired off targets effects, and therefore, a critical risk-benefit evaluation is required. The present review discusses the current state-of-the-art on the identification of viral host dependency factors (HDF) and the workflow required for the development of HDT as antivirals. Then, we focus on the feasibility of using a specific class of host factors, those involved in innate immune modulation, as broad-spectrum antiviral therapeutic strategies. Finally, a brief summary of major roadblocks derived from targeting host cellular proteins and putative future strategies to overcome its major limitations is proposed.

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“…The latter comprises GP1, the receptorbinding subunit, and GP2, the fusion subunit. Following internalization of the virus by macropinocytosis, and possibly by clathrin-or caveolin-mediated endocytosis [123,125], GP1 is cleaved by cathepsins B and L in endosomes, and the cleaved form (GPcl) binds the endosomal cholesterol transporter protein, Niemann-Pick C1. This interaction, however, does not appear to be sufficient to induce membrane fusion [124].…”

Section: Peptides It1b and Meln4 Designed To Have Membrane "Interfaci...mentioning

confidence: 99%

Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design

2021

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Fusion of lipid-enveloped viruses with the cellular plasma membrane or the endosome membrane is mediated by viral envelope proteins that undergo large conformational changes following binding to receptors. The HIV-1 fusion protein gp41 undergoes a transition into a “six-helix bundle” after binding of the surface protein gp120 to the CD4 receptor and a co-receptor. Synthetic peptides that mimic part of this structure interfere with the formation of the helix structure and inhibit membrane fusion. This approach also works with the S spike protein of SARS-CoV-2. Here we review the peptide inhibitors of membrane fusion involved in infection by influenza virus, HIV-1, MERS and SARS coronaviruses, hepatitis viruses, paramyxoviruses, flaviviruses, herpesviruses and filoviruses. We also describe recent computational methods used for the identification of peptide sequences that can interact strongly with protein interfaces, with special emphasis on SARS-CoV-2, using the PePI-Covid19 database.

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Structural and Functional Aspects of Ebola Virus Proteins

Cited by 44 publications

References 212 publications

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

Protein Folding Interdiction Strategy for Therapeutic Drug Development in Viral Diseases: Ebola VP40 and Influenza A M1

Viral-Host Dependency Factors as Therapeutic Targets to Overcome Antiviral Drug-Resistance: A Focus on Innate Immune Modulation

Inhibition of Viral Membrane Fusion by Peptides and Approaches to Peptide Design

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