Viruses . Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)

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Viruses


. 2020 Jun 10;12(6):E628.
doi: 10.3390/v12060628.
Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)


Shuofeng Yuan ¹ , Chris Chun-Yiu Chan ¹ , Kenn Ka-Heng Chik ¹ , Jessica Oi-Ling Tsang ¹ , Ronghui Liang ¹ , Jianli Cao ¹ , Kaiming Tang ¹ , Jian-Piao Cai ¹ , Zi-Wei Ye ¹ , Feifei Yin ² , Kelvin Kai-Wang To ¹ , Hin Chu ¹ , Dong-Yan Jin ³ , Ivan Fan-Ngai **** ⁴ , Kwok-Yung Yuen ^{1 2} , Jasper Fuk-Woo Chan ^{1 2}



Affiliations

• PMID: 32532085
• DOI: 10.3390/v12060628

Free article

Abstract

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-β1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC₅₀ at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.

Keywords: 25-hydroxycholesterol; AM580; COVID-19; coronavirus; interferon; treatment.