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Repositioning anticancer drugs as novel COVID-19 antivirals: targeting structural and functional similarities between viral proteins and cancer

Part of: Molecular understanding of Covid pathogenesis, immunity and therapeutics

Published online by Cambridge University Press:  22 April 2022

Zheng Yao Low Open the ORCID record for Zheng Yao Low [Opens in a new window] ,
Ashley Jia Wen Yip Open the ORCID record for Ashley Jia Wen Yip [Opens in a new window]  and
Sunil Kumar Lal Open the ORCID record for Sunil Kumar Lal [Opens in a new window]
Zheng Yao Low
Affiliation:
School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
Ashley Jia Wen Yip
Affiliation:
School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
Sunil Kumar Lal*
Affiliation:
School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia Tropical Medicine and Biology Platform, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
*
Author for correspondence: Sunil Kumar Lal, E-mail: sunil.lal@monash.edu
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Abstract

The current COVID-19 pandemic contributed by the SARS-CoV-2 has put in place an urgent need for new and promising antiviral therapeutics. The viral RNA-dependent RNA polymerase (RdRp) enzyme plays a vital role in viral replication for all RNA viruses, including SARS-CoV-2, thereby making it a prime and promising candidate for novel antiviral targeting. Interestingly, the human telomerase reverse transcriptase (hTERT), a common catalytic subunit of the telomerase enzyme in many cancers, has also been identified with structural and functional similarities to the viral RdRp. Therefore, it becomes essential to evaluate and consider anticancer drugs that target hTERT towards antiviral RdRp activity, and vice versa. For instance, Floxuridine, an hTERT inhibitor, and VX-222, a hepatitis C virus RdRp inhibitor, are now gaining recognition as a potential antiviral against SARS-CoV-2 and anti-hTERT for cancer, simultaneously. While limited studies on hTERT inhibitors for use as viral RdRp, and anti-RdRp inhibitors as hTERT inhibitors are available, in this review, we aim at bringing to light this close structural and functional relationship between both these enzymes. We punctuate this idea with specific examples on how potential anticancer inhibitors can effectively be brought to use as inhibitors against the SARS-CoV-2 virus, a relatively new pathogen, compared to the very well-studied field of cancer research.

Keywords

AnticancerantiviralcancerCOVID-19drug repositioningdrug repurposinghTERTinhibitionRdRpSARS-CoV-2virus
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 24 , 2022 , e20
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press

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