
A deep learning-based framework can efficiently generate novel antimicrobial peptides with potent activities against both bacteria and viruses.


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Antimicrobial peptides (AMPs) are attractive candidates to combat antibiotic resistance for their capability to target bio-membranes and restrict a wide range of pathogens. It is a daunting challenge to discover novel AMPs due to their sparse distributions in a vast peptide universe, especially for peptides that demonstrate potencies for both bacterial membranes and viral envelopes. Here we establish a de novo AMP design framework by bridging a deep generative module and a graph-encoding activity regressor. The generative module learns hidden ‘grammars’ of AMP features and produces candidates sequentially pass antimicrobial predictor and antiviral classifiers. We discover three bifunctional AMPs and experimentally validated their abilities to inhibit a spectrum of pathogens in vitro and in animal models. Notably, P076 is a highly potent bactericide with the minimal inhibitory concentration of 0.21 μM against multidrug-resistant A. baumannii , while P002 broadly inhibits five enveloped viruses. Our study provides feasible means to uncover sequences that simultaneously encode antimicrobial and antiviral activities, thus bolstering the function spectra of AMPs to combat a wide range of drug-resistant infections.

### Competing Interest Statement

The authors have declared no competing interest.

Exploring the repository of de novo designed bifunctional antimicrobial peptides through deep learning

computational-discovery-and-experimental-validation-of-potent-bifunctional-antimicrobial-peptides


Computational Discovery and Experimental Validation of Potent Bifunctional Antimicrobial Peptides
