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      Pandemic Preparedness: The Singapore Drug Repurposing Antiviral Strategy

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            Abstract

            Pandemic preparedness is a global imperative, given the recurring threats posed by emerging infectious diseases. Traditional drug development and discovery has not kept pace with threats from emerging and re-emerging viral diseases such as the mosquito-borne Chikungunya, Zika and Dengue viruses, monkey pox, Ebola virus, MERSCoV and more recently, SARS-CoV-2. The unpredictability of pandemic viral pathogens demands adaptable approaches to counter their impact on public health. Drug repurposing offers a versatile and timely response to such crises. Re-evaluation of existing pharmaceuticals for their potential efficacy against viral pathogens, healthcare systems can expedite the development of therapeutics and preventive measures. By using an integrated systemwide approaches and technology driven platforms including genome-wide gene silencing profiling, miRNA profiling and proteomics via high-throughput assays, combined with bio-imaging and computational biology, we attempt to understand the biological complexity of virus-host interactions and translating it into effective antiviral strategies against these viral pathogens. To address the urgent need for treatment options, we have evaluated an array of antiviral strategies from high throughput screening and drug repurposing for potential antiviral therapeutics against these viruses, to the utilization of molecular intervention as well as the development of next generation live attenuated virus vaccines. The in-vivo efficacy of these antiviral approaches is also illustrated with murine models established for these viral infections. Finally, the availability and support from high containment facilities such as BSL2-enhanced and BSL3/ABSL3 core facilities are essential to manage the pharmacological research for these high-risk viral pathogens. Together, these studies have provided the basis for the rapid development of effective antiviral approaches that can be clinically validated and are crucial for enhancing our collective resilience against ongoing challenges of pandemic and future health threats caused by viral pathogens.

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            Author and article information

            Conference
            REPO4EU
            12 September 2023
            Affiliations
            [1 ] Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore ( https://ror.org/01tgyzw49)
            Author information
            https://orcid.org/0000-0002-1673-6819
            Article
            10.58647/REXPO.23003
            25b4241e-623f-4172-8d3b-fee397a063e0
            Authors

            Published under Creative Commons Attribution 4.0 International ( CC BY 4.0). Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source.

            RExPO23
            2
            Stockholm, Sweden
            25-26 October 2023
            History
            Product

            REPO4EU

            Categories

            Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
            Pharmacology & Pharmaceutical medicine
            Pandemic preparedness,antiviral therapeutics,medically important viruses,high-throughput screens,mosquitoborne flaviviruses,Mosquito borne alphaviruses,human enteroviruses,coronaviruses,biosafety level 3 facility,invivo efficacy

            References

            1. Wu Kan Xing, Yogarajah Thinesshwary, Loe Marcus Wing Choy, Kaur Parveen, Lee Regina Ching Hua, Mok Chee Keng, Wong Yi Hao, Phuektes Patchara, Yeo Li Sze, Chow Vincent T.K., Tan Yong Wah, Chu Justin Jang Hann. The host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses. Acta Pharmaceutica Sinica B. Vol. 13(5):2039–2055. 2023. Elsevier BV. [Cross Ref]

            2. Loe Marcus Wing Choy, Lee Regina Ching Hua, Chu Justin Jang Hann. Antiviral activity of the FDA-approved drug candesartan cilexetil against Zika virus infection. Antiviral Research. Vol. 172:2019. Elsevier BV. [Cross Ref]

            3. Ng Yan Ling, Salim Cyrill Kafi, Chu Justin Jang Hann. Drug repurposing for COVID-19: Approaches, challenges and promising candidates. Pharmacology & Therapeutics. Vol. 228:2021. Elsevier BV. [Cross Ref]

            4. Sun Jialei, Yogarajah Thinesshwary, Lee Regina Ching Hua, Kaur Parveen, Inoue Masafumi, Tan Yong Wah, Chu Justin Jang Hann. Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications. Scientific Reports. Vol. 10(1)2020. Springer Science and Business Media LLC. [Cross Ref]

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