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Article

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

1
State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
2
Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong, China
3
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
4
Division of Infectious Diseases, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 7 May 2020 / Revised: 8 June 2020 / Accepted: 8 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue Drug-Repositioning Opportunities for Antiviral Therapy)
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. View Full-Text
Keywords: coronavirus; COVID-19; interferon; AM580; 25-hydroxycholesterol; treatment coronavirus; COVID-19; interferon; AM580; 25-hydroxycholesterol; treatment
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Figure 1

MDPI and ACS Style

Yuan, S.; Chan, C.C.-Y.; Chik, K.K.-H.; Tsang, J.O.-L.; Liang, R.; Cao, J.; Tang, K.; Cai, J.-P.; Ye, Z.-W.; Yin, F.; To, K.K.-W.; Chu, H.; Jin, D.-Y.; Hung, I.F.-N.; Yuen, K.-Y.; Chan, J.F.-W. Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19). Viruses 2020, 12, 628. https://0-doi-org.brum.beds.ac.uk/10.3390/v12060628

AMA Style

Yuan S, Chan CC-Y, Chik KK-H, Tsang JO-L, Liang R, Cao J, Tang K, Cai J-P, Ye Z-W, Yin F, To KK-W, Chu H, Jin D-Y, Hung IF-N, Yuen K-Y, Chan JF-W. Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19). Viruses. 2020; 12(6):628. https://0-doi-org.brum.beds.ac.uk/10.3390/v12060628

Chicago/Turabian Style

Yuan, Shuofeng, Chris Chun-Yiu Chan, Kenn Ka-Heng Chik, Jessica Oi-Ling Tsang, Ronghui Liang, Jianli Cao, Kaiming Tang, Jian-Piao Cai, Zi-Wei Ye, Feifei Yin, Kelvin Kai-Wang To, Hin Chu, Dong-Yan Jin, Ivan Fan-Ngai Hung, Kwok-Yung Yuen, and Jasper Fuk-Woo Chan. 2020. "Broad-Spectrum Host-Based Antivirals Targeting the Interferon and Lipogenesis Pathways as Potential Treatment Options for the Pandemic Coronavirus Disease 2019 (COVID-19)" Viruses 12, no. 6: 628. https://0-doi-org.brum.beds.ac.uk/10.3390/v12060628

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