The Role of Protein Disorder in Nuclear Transport and in Its Subversion by Viruses

Wubben, Jacinta M.; Atkinson, Sarah C.; Borg, Natalie A.

doi:10.3390/cells9122654

Cited by 22 publications

(26 citation statements)

References 189 publications

(130 reference statements)

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“…These results are within the ranges reported of inhibition of activity (IC 50 = 0.12–0.5 μM) and kinetics of the Helicase (IC 50 = 0.019–0.354 μM), as well as viral replication by 50% (IC 50 = 0.0005–4 μM) [ 81 ]. Observations that are related to the alteration of viral replication that this compound can induce through this pathway, since ivermectin has also been shown to bind to this non-structural viral protein [ 82 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González

Hurtado-León

Lossada

et al. 2021

Biophysical Chemistry

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The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro . However, there are few reports on the behavior of each homolog. We investigated the interaction of each homolog with promising targets of interest associated with SARS-CoV-2 infection from a biophysical and computational-chemistry perspective using docking and molecular dynamics. We observed a differential behavior for each homolog, with an affinity of HB1b for viral structures, and of HB1a for host structures considered. The induced disturbances were differential and influenced by the hydrophobicity of each homolog and of the binding pockets. We present the first comparative analysis of the potential theoretical inhibitory effect of both avermectins on biomolecules associated with COVID-19, and suggest that ivermectin through its homologs, has a multiobjective behavior.

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Section: Resultsmentioning

confidence: 99%

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González

Hurtado-León

Lossada

et al. 2021

Biophysical Chemistry

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“…The role of the cleavage/degradation of the NPC during infection with Flavivirus is still unknown [ 12 ]. However, during infection with other RNA-viruses such as Poliovirus and Rhinovirus, the degradation of nucleoporins has been associated with the inhibition of the import/export of transcription factors, mRNAs, and immune response modulation to guarantee viral replication [ 75 ].…”

Section: Alterations Of the Npc By Ns2b-3 Protease Of Flavivirus : The Cleavage Of The Complexmentioning

confidence: 99%

The Nuclear Pore Complex Is a Key Target of Viral Proteases to Promote Viral Replication

Jesús-González

Palacios-Rápalo

Reyes-Ruiz

et al. 2021

Viruses

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Various viruses alter nuclear pore complex (NPC) integrity to access the nuclear content favoring their replication. Alteration of the nuclear pore complex has been observed not only in viruses that replicate in the nucleus but also in viruses with a cytoplasmic replicative cycle. In this last case, the alteration of the NPC can reduce the transport of transcription factors involved in the immune response or mRNA maturation, or inhibit the transport of mRNA from the nucleus to the cytoplasm, favoring the translation of viral mRNAs or allowing access to nuclear factors necessary for viral replication. In most cases, the alteration of the NPC is mediated by viral proteins, being the viral proteases, one of the most critical groups of viral proteins that regulate these nucleus–cytoplasmic transport changes. This review focuses on the description and discussion of the role of viral proteases in the modification of nucleus–cytoplasmic transport in viruses with cytoplasmic replicative cycles and its repercussions in viral replication.

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“…Following genome release into the cytosol, viral genomic RNA is uncoated and translated for the synthesis of non-structural viral proteins. Importantly, this intrinsic disorganization of viral proteins is an inherent feature and a strategy of viruses to disrupt host nucleocytoplasmic transport to benefit their own replication [ 48 ]. Viral RNA is then replicated and subgenomic RNAs are translated in double-membrane vesicles, as previously reported in several viruses, including coronavirus [ 49 , 50 , 51 , 52 ].…”

Section: The Life Cycle Of Sars-cov-2mentioning

confidence: 99%

Epigenetic Mechanisms Underlying COVID-19 Pathogenesis

et al. 2021

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In 2019, a novel severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported and was declared a pandemic by the World Health Organization (WHO) in March 2020. With the advancing development of COVID-19 vaccines and their administration globally, it is expected that COVID-19 will converge in the future; however, the situation remains unpredictable because of a series of reports regarding SARS-CoV-2 variants. Currently, there are still few specific effective treatments for COVID-19, as many unanswered questions remain regarding the pathogenic mechanism of COVID-19. Continued elucidation of COVID-19 pathogenic mechanisms is a matter of global importance. In this regard, recent reports have suggested that epigenetics plays an important role; for instance, the expression of angiotensin I converting enzyme 2 (ACE2) receptor, an important factor in human infection with SARS-CoV-2, is epigenetically regulated; further, DNA methylation status is reported to be unique to patients with COVID-19. In this review, we focus on epigenetic mechanisms to provide a new molecular framework for elucidating the pathogenesis of SARS-CoV-2 infection in humans and of COVID-19, along with the possibility of new diagnostic and therapeutic strategies.

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The Role of Protein Disorder in Nuclear Transport and in Its Subversion by Viruses

Cited by 22 publications

References 189 publications

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

The Nuclear Pore Complex Is a Key Target of Viral Proteases to Promote Viral Replication

Epigenetic Mechanisms Underlying COVID-19 Pathogenesis

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