In-Silico Approaches for the Screening and Discovery of Broad-Spectrum Marine Natural Product Antiviral Agents Against Coronaviruses

The urgent need for SARS-CoV-2 controls has led to a reassessment of approaches to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. There are yet no clinically approved broad-spectrum antivirals available for beta-coronaviruses. Discovery pipelines for pan-virus medications against a broad range of betacoronaviruses are therefore a priority. A variety of marine natural product (MNP) small molecules have shown inhibitory activity against viral species. Access to large data caches of small molecule structural information is vital to finding new pharmaceuticals. Increasingly, molecular docking simulations are being used to narrow the space of possibilities and generate drug leads. Combining in-silico methods, augmented by metaheuristic optimization and machine learning (ML) allows the generation of hits from within a virtual MNP library to narrow screens for novel targets against coronaviruses. In this review article, we explore current insights and techniques that can be leveraged to generate broad-spectrum antivirals against betacoronaviruses using in-silico optimization and ML. ML approaches are capable of simultaneously evaluating different features for predicting inhibitory activity. Many also provide a semi-quantitative measure of feature relevance and can guide in selecting a subset of features relevant for inhibition of SARS-CoV-2.

Automated summary

The urgent need to control SARS-CoV-2 has led to a reassessment of methods for identifying and developing natural product inhibitors for highly virulent and rapidly emerging viruses. Currently, there are no approved broad-spectrum antivirals for beta-coronaviruses. Marine natural product small molecules have shown inhibitory activity against viral species. Molecular docking simulations, augmented by metaheuristic optimization and machine learning, can help generate hits from a virtual library to narrow down screens for novel targets against coronaviruses. In this review, we explore current insights and techniques for generating broad-spectrum antivirals against betacoronaviruses using in-silico optimization and machine learning.