Version 1
: Received: 28 March 2020 / Approved: 30 March 2020 / Online: 30 March 2020 (03:34:26 CEST)
Version 2
: Received: 6 January 2021 / Approved: 8 January 2021 / Online: 8 January 2021 (13:53:55 CET)
How to cite:
Nordor, A.V.; Siwo, G.H. Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA. Preprints2020, 2020030437. https://doi.org/10.20944/preprints202003.0437.v1
Nordor, A.V.; Siwo, G.H. Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA. Preprints 2020, 2020030437. https://doi.org/10.20944/preprints202003.0437.v1
Nordor, A.V.; Siwo, G.H. Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA. Preprints2020, 2020030437. https://doi.org/10.20944/preprints202003.0437.v1
APA Style
Nordor, A.V., & Siwo, G.H. (2020). Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA. Preprints. https://doi.org/10.20944/preprints202003.0437.v1
Chicago/Turabian Style
Nordor, A.V. and Geoffrey H. Siwo. 2020 "Predicting Broad-Spectrum Antiviral Drugs against RNA Viruses Using Transcriptional Responses to Exogenous RNA" Preprints. https://doi.org/10.20944/preprints202003.0437.v1
Abstract
All RNA viruses deliver their genomes into target host cells through processes distinct from normal trafficking of cellular RNA transcripts. The delivery of viral RNA into most cells hence triggers innate antiviral defenses that recognize viral RNA as foreign. In turn, viruses have evolved mechanisms to subvert these defenses, allowing them to thrive in target cells. Therefore, drugs activating defense to foreign or exogenous RNA could serve as broad-spectrum antiviral drugs. Here we show that transcriptional signatures associated with cellular responses to the delivery of a non-viral exogenous RNA sequence into human cells predicts small molecules with broad-spectrum antiviral activity. In particular, transcriptional responses to the delivery of cas9 mRNA into human hematopoietic stem and progenitor cells (HSPCs) highly matches those triggered by small molecules with broad-spectrum antiviral activity such as emetine, homoharringtonine, pyrvinium pamoate and anisomycin, indicating that these drugs are potentially active against other RNA viruses. Furthermore, these drugs have been approved for other indications and could thereby be repurposed to novel viruses. We propose that the antiviral activity of these drugs to SARS-CoV-2 should therefore be determined as they have been shown as active against other coronaviruses including SARS-CoV and MERS-CoV. These drugs could also be explored as potential adjuvants to COVID-19 vaccines in development due to their potential effect on the innate antiviral defenses that could bolster adaptive immunity when delivered alongside vaccine antigens.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
