Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing

Vautrin, Audrey; Manchon, Laurent; Garcel, Aude; Campos, Noëlie; Lapasset, Laure; Laaref, Abdelhamid Mahdi; Bruno, Roman; Gislard, Marie; Dubois, Emeric; Scherrer, Didier; Ehrlich, J Hartmut; Tazi, Jamal

doi:10.1038/s41598-018-37813-y

Cited by 49 publications

(33 citation statements)

References 68 publications

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“…Likewise, ncRNAs such as miR-576-3p have been shown to be involved in STING’s operation ( 162 , 163 ). Another investigated agent undergoing trials for COVID-19, ABX-464 (Abivax SA, clinical trial identifier NCT04393038), has been shown to upregulate the expression of miR-124 in other infectious contexts ( 164 ). Cholinergic signaling has also been found to regulate miR-124, with corresponding effects in inflammation signature pathways of STAT3, IL-6 and TNFa ( 122 ).…”

Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

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Section: Discussionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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“…Whether or not it can do so successfully in the case of COVID-19 is a matter for further research, 73,74 but presently there is research being conducted by institutions worldwide, which seek to find medicines and/or medicine regimens that possess simultaneous capacities for antiviral and anti-inflammatory actions, in line with such principles. 73,101,102…”

Section: Meditation and Yoga As Adjunctive Treatment 549mentioning

confidence: 99%

Meditation and Yoga Practices as Potential Adjunctive Treatment of SARS-CoV-2 Infection and COVID-19: A Brief Overview of Key Subjects

Bushell

Castle

Williams

et al. 2020

The Journal of Alternative and Complementary Medicine

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Editor's Note: As an acute condition quickly associated with multiple chronic susceptibilities, COVID-19 has rekindled interest in, and controversy about, the potential role of the host in disease processes. While hundreds of millions of research dollars have been funneled into drug and vaccine solutions that target the external agent, integrative practitioners tuned to enhancing immunity faced a familiar mostly unfunded task. First, go to school on the virus. Then draw from the global array of natural therapies and practices with host-enhancing or anti-viral capabilities to suggest integrative treatment strategies. The near null-set of conventional treatment options propels this investigation. In this paper, researchers from the

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“…52,52,54 ABX464-It is an investigational drug having both antiinflammatory and antiviral activity by interfering with pre mRNA splicing and have been investigated for a wide range of diseases such as HIV, Ulcerative colitis, COVID 19 and Rheumatoid arthritis etc. 55,56,57,58 A wide array of molecules have been developed for the therapy of HIV infections. Yet, we are still away from developing a complete cure from this long ailing morbid and mortal condition.…”

Section: Attachment Inhibitor-mentioning

confidence: 99%

A Concise Review of Existing Therapies and Recent Advances in the Management of HIV Infection

Lal¹,

Kumar²,

Dutta³

et al. 2020

IJPSRR

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Human immunodeficiency virus (HIV) is an RNA retrovirus capable of replicating its genome by the DNA dependent RNA polymerase (DdRp). The virus infects the lymphocytes with the help of viral glycoproteins like Gp 120 and Gp 41. The entry of virus leads to the release of viral RNA inside the host cell, which is further replicated, and assembly of virion particles leads to the release of viral particles that further infect the other host cells. Established therapies include those that inhibit the entry of virus in the host cell, those inhibiting the integrase activity, those acting as protease inhibitors and also we have Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) with NRTIS being the competitive inhibitors of DdRp also show mitochondrial toxicity. Protease inhibitors are known for their adverse effect profile and several drug interactions due to their enzyme inhibitory property. The most effective approach in the management is the highly active antiretroviral therapy containing the combined use of drugs having varied mechanisms of action. Still, long term use of these agents can end up in resistance against these agents. Well documented adverse effect profile along with various drug interactions associated with anti-HIV drugs mandates the need for the development of newer drugs against HIV. Newer molecules provide a better safety profile and better alternatives for drug-resistant cases. Therefore, this review focuses on existing therapies along with various newer pipeline drugs with their mechanisms and advantages over the existing therapies.

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Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing

Cited by 49 publications

References 68 publications

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

Meditation and Yoga Practices as Potential Adjunctive Treatment of SARS-CoV-2 Infection and COVID-19: A Brief Overview of Key Subjects

A Concise Review of Existing Therapies and Recent Advances in the Management of HIV Infection

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