# A Novel Framework Integrating AI Model and Enzymological Experiments Promotes Identification of SARS-CoV-2 3CL Protease Inhibitors and Activity-based Probe

arXiv: https://arxiv.org/abs/2105.14224 · HTML: https://mlsanity.com/paper/2105.14224/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 11 of its 56 references that are in the map.
- First posted on arXiv 29 May 2021.

## Builds on (most cited first, 11 of 11)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Learning Phrase Representations using RNN Encoder-Decoder for Statistical Machine Translation](https://mlsanity.com/paper/1406.1078/) (2014)
- [Fast and Accurate Deep Network Learning by Exponential Linear Units (ELUs)](https://mlsanity.com/paper/1511.07289/) (2015)
- [Recent Trends in Deep Learning Based Natural Language Processing](https://mlsanity.com/paper/1708.02709/) (2017)
- [Evaluating Protein Transfer Learning with TAPE](https://mlsanity.com/paper/1906.08230/) (2019)
- [DeepDTA: Deep Drug-Target Binding Affinity Prediction](https://mlsanity.com/paper/1801.10193/) (2018)
- [Protein-Ligand Scoring with Convolutional Neural Networks](https://mlsanity.com/paper/1612.02751/) (2016)
- [Development and evaluation of a deep learning model for protein-ligand binding affinity prediction](https://mlsanity.com/paper/1712.07042/) (2017)
- [AtomNet: A Deep Convolutional Neural Network for Bioactivity Prediction in Structure-based Drug Discovery](https://mlsanity.com/paper/1510.02855/) (2015)

## Built on by (most cited first, 1 of 1)

- [Bridging the gap between target-based and cell-based drug discovery with a graph generative multi-task model](https://mlsanity.com/paper/2208.04944/) (2022)

## Abstract (arXiv)

The identification of protein-ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here we propose a novel framework, named AIMEE, integrating AI Model and Enzymology Experiments, to identify inhibitors against 3CL protease of SARS-CoV-2, which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value less than 3 μM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and expanding the boundaries of drug discovery.