Evidence map›Paper›PMID 36711787›Full record

ArticlebioRxiv : the preprint server for biology2023

Broad-spectrum antiviral inhibitors targeting pandemic potential RNA viruses.

Gustavo Garcia, Joseph Ignatius Irudayam, Arjit Vijay Jeyachandran, Swati Dubey, Christina Chang, Sebastian Castillo Cario, Nate Price, Sathya Arumugam, Angelica L Marquez, Aayushi Shah and 8 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 2 countries.

Gustavo GarciaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Joseph Ignatius IrudayamDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Arjit Vijay JeyachandranDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Swati DubeyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Christina ChangDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Sebastian Castillo CarioDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Nate PriceDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Sathya ArumugamDepartment of Mathematics, Government College Daman, U.T of DNH & DD, India.
Angelica L MarquezDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Aayushi ShahDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Amir FanaeiDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Nikhil ChakravartyDepartment of Epidemiology, University of California, Los Angeles, Los Angeles, CA, USA.
Shantanu JoshiDepartment of Neurology, University of California, Los Angeles, CA, USA.
Sanjeev SinhaAll India Institute of Medical Sciences, New Delhi, India.
Samuel W FrenchJonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
Mark ParcellsDepartment of Animal and Food Sciences, Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Arunachalam RamaiahTata Institute for Genetics and Society, Center at inStem, Bangalore 560065, India.
Vaithilingaraja ArumugaswamiDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
University of California, Los Angeles · USAll India Institute of Medical Sciences · INCalifornia NanoSystems Institute · USInstitute for Stem Cell Biology and Regenerative Medicine · INUCLA Jonsson Comprehensive Cancer CenterUniversity of Delaware · US

Funding

Metabolic and epigenetic reprogramming of vital organs in SARS-CoV-2 induced systemic toxicityR01DK132735 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARUMUGASWAMI, VAITHILINGARAJA, DEB, ARJUN · 2021 to 2023
$6.0M
Interplay between AMPK and Hippo Signaling Regulates Ocular Antiviral Response to Zika virus infectionR01EY032149 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Vaithilingaraja Arumugaswami, Ashok Kumar · 2021 to 2026
$2.8M
Developing three-dimensional antisense oligonucleotide drugs against COVID-19R01AI163216 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GUO, FENG · 2021 to 2025
$2.3M
NEI NIH HHS R01 EY032149NIAID NIH HHS R01 AI163216NIDDK NIH HHS R01 DK132735
6 · The paper itself

Abstract

RNA viruses continue to remain a clear and present threat for potential pandemics due to their rapid evolution. To mitigate their impact, we urgently require antiviral agents that can inhibit multiple families of disease-causing viruses, such as arthropod-borne and respiratory pathogens. Potentiating host antiviral pathways can prevent or limit viral infections before escalating into a major outbreak. Therefore, it is critical to identify broad-spectrum antiviral agents. We have tested a small library of innate immune agonists targeting pathogen recognition receptors, including TLRs, STING, NOD, Dectin and cytosolic DNA or RNA sensors. We observed that TLR3, STING, TLR8 and Dectin-1 ligands inhibited arboviruses, Chikungunya virus (CHIKV), West Nile virus (WNV) and Zika virus, to varying degrees. Cyclic dinucleotide (CDN) STING agonists, such as cAIMP, diABZI, and 2',3'-cGAMP, and Dectin-1 agonist scleroglucan, demonstrated the most potent, broad-spectrum antiviral function. Comparative transcriptome analysis revealed that CHIKV-infected cells had larger number of differentially expressed genes than of WNV and ZIKV. Furthermore, gene expression analysis showed that cAIMP treatment rescued cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provided protection against CHIKV in a CHIKV-arthritis mouse model. Cardioprotective effects of synthetic STING ligands against CHIKV, WNV, SARS-CoV-2 and enterovirus D68 (EV-D68) infections were demonstrated using human cardiomyocytes. Interestingly, the direct-acting antiviral drug remdesivir, a nucleoside analogue, was not effective against CHIKV and WNV, but exhibited potent antiviral effects against SARS-CoV-2, RSV (respiratory syncytial virus), and EV-D68. Our study identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses, which can be rapidly deployed to prevent or mitigate future pandemics.

Identifiers

PMID36711787
PMCPMC9882367
OpenAlexW4317693910

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.