Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants
Chee-Keng Mok,
Yan Ling Ng,
Bintou Ahmadou Ahidjo,
Zhen Qin Aw,
Huixin Chen,
Yi Hao Wong,
Regina Ching Hua Lee,
Marcus Wing Choy Loe,
Jing Liu,
Kai Sen Tan,
Parveen Kaur,
De Yun Wang,
Erwei Hao,
Xiaotao Hou,
Yong Wah Tan,
Jiagang Deng,
Justin Jang Hann Chu
Affiliations
Chee-Keng Mok
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Yan Ling Ng
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Bintou Ahmadou Ahidjo
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Zhen Qin Aw
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Huixin Chen
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Yi Hao Wong
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Regina Ching Hua Lee
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Marcus Wing Choy Loe
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
Jing Liu
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Kai Sen Tan
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
Parveen Kaur
Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore
De Yun Wang
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Erwei Hao
Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
Xiaotao Hou
Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
Yong Wah Tan
Collaborative and Translation Unit for HFMD, Institute of Molecular and Cell Biology, Singapore 138673, Singapore
Jiagang Deng
Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, China
Justin Jang Hann Chu
Biosafety Level 3 Core Facility, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.
