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Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since 2019, spreading rapidly and posing a significant threat to human health and life. With over 6 billion confirmed cases of the virus, the need for effective therapeutic drugs has become more urgent than ever before. RNA-dependent RNA polymerase (RdRp) is crucial in viral replication and transcription, catalysing viral RNA synthesis and serving as a promising therapeutic target for developing antiviral drugs. In this article, we explore the inhibition of RdRp as a potential treatment for viral diseases, analysing the structural information of RdRp in virus proliferation and summarizing the reported inhibitors’ pharmacophore features and structure–activity relationship profiles. We hope that the information provided by this review will aid in structure-based drug design and aid in the global fight against SARS-CoV-2 infection.

Graphical Abstract

Highlights

  • Exploring the potential clinical targets for attenuating coronavirus disease 2019 (COVID-19) by structure-based drug designing of RdRp inhibitors.

  • RdRp catalytic site and druggable cavities predictions of SARS-CoV-2.

  • Pharmacophoric features and structure–activity relationship analysis of different repurposed therapeutic drugs for COVID-19 against RdRp of SARS-CoV-2.

  • Current treatments are logistically challenging, increasing the need for safe and effective oral therapies.

  • Ongoing global efforts to prevent the spread of COVID-19 disease and the current status of SARS-CoV-2.

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Data availability statement

The data supporting this work is available in this paper, and all other details are present in the supporting information. Furthermore, the data supporting this study are available from the corresponding author upon reasonable request.

Abbreviations

EUA:

Emergency Use Authorization

FDA:

Food and Drug Administration

ACE2:

Angiotensin-converting enzyme 2

NHC:

N4-hydroxycytidine

RSV:

Respiratory syncytial virus

TNF-α:

Tumour necrosis factor α

ExoN:

Exoribonuclease

CTP:

Cytidine triphosphate

HBD:

Hydrogen-bond donors

HBA:

Hydrogen-bond acceptors

NiRAN:

Nidovirus RdRp-associated nucleotidyl transferase

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (32201053) and the Beijing Institute of Technology Research Fund Program for Young Scholars (3100012222222). The image of the graphical abstract was created with tools obtained from BioRender.com.

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Authors and Affiliations

  1. Key Laboratory of Medical Molecule Science and Pharmaceutical Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 10081, China

    Kiran Shehzadi, Afsheen Saba, Mingjia Yu & Jianhua Liang

  2. Yangtze Delta Region Academy of Beijing Institute of Technology, Jiaxing, 314019, China

    Jianhua Liang

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  1. Kiran Shehzadi
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  2. Afsheen Saba
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  3. Mingjia Yu
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Shehzadi, K., Saba, A., Yu, M. et al. Structure-Based Drug Design of RdRp Inhibitors against SARS-CoV-2. Top Curr Chem (Z) 381, 22 (2023). https://doi.org/10.1007/s41061-023-00432-x

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