tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Chris Chun-Yiu Chan[SUP] 1 [/SUP], Kenn Ka-Heng Chik[SUP] 1 [/SUP], Jessica Oi-Ling Tsang[SUP] 1 [/SUP], Ronghui Liang[SUP] 1 [/SUP], Jianli Cao[SUP] 1 [/SUP], Kaiming Tang[SUP] 1 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 1 [/SUP], Feifei Yin[SUP] 2 [/SUP], Kelvin Kai-Wang To[SUP] 1 [/SUP], Hin Chu[SUP] 1 [/SUP], Dong-Yan Jin[SUP] 3 [/SUP], Ivan Fan-Ngai ****[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 1 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 [/SUP]
Affiliations
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 EC[SUB]50[/SUB] 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.
. 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[SUP] 1 [/SUP], Chris Chun-Yiu Chan[SUP] 1 [/SUP], Kenn Ka-Heng Chik[SUP] 1 [/SUP], Jessica Oi-Ling Tsang[SUP] 1 [/SUP], Ronghui Liang[SUP] 1 [/SUP], Jianli Cao[SUP] 1 [/SUP], Kaiming Tang[SUP] 1 [/SUP], Jian-Piao Cai[SUP] 1 [/SUP], Zi-Wei Ye[SUP] 1 [/SUP], Feifei Yin[SUP] 2 [/SUP], Kelvin Kai-Wang To[SUP] 1 [/SUP], Hin Chu[SUP] 1 [/SUP], Dong-Yan Jin[SUP] 3 [/SUP], Ivan Fan-Ngai ****[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 1 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 [/SUP]
Affiliations
- PMID: 32532085
- DOI: 10.3390/v12060628
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 EC[SUB]50[/SUB] 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.