Recent advances in chemometric modelling of inhibitors against SARS-CoV-2

Abstract

The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great harm to all countries worldwide. This disease can be prevented by vaccination and managed using various treatment methods, including injections, oral medications, or aerosol therapies. However, the selection of suitable compounds for the research and development of anti-SARS-CoV-2 drugs is a daunting task because of the vast databases of available compounds. The traditional process of drug research and development is time-consuming, labour-intensive, and costly. The application of chemometrics can significantly expedite drug R&D. This is particularly necessary and important for drug development against pandemic public emergency diseases, such as COVID-19. Through various chemometric techniques, such as quantitative structure-activity relationship (QSAR) modelling, molecular docking, and molecular dynamics (MD) simulations, compounds with inhibitory activity against SARS-CoV-2 can be quickly screened, allowing researchers to focus on the few prioritised candidates. In addition, the ADMET properties of the screened candidate compounds should be further explored to promote the successful discovery of anti-SARS-CoV-2 drugs. In this case, considerable time and economic costs can be saved while minimising the need for extensive animal experiments, in line with the 3R principles. This paper focuses on recent advances in chemometric modelling studies of COVID-19-related inhibitors, highlights current limitations, and outlines potential future directions for development.

Highlights

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  QSAR models of SARS-CoV-2 main protease (3CLpro) inhibitors are summarised.

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  QSAR models of spike protein and hACE2 inhibitors are summarised.

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  Molecular docking, molecular dynamics and ADMET predictions are involved.

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  The potential SARS-CoV-2 inhibitor candidates for each target are provided.

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  RdRp and PLpro are also potential targets for SARS-CoV-2 inhibitor development.