Molecular De-extinction And Amr
Written by Ayebamiebi Yousuo
Introduction
Could this be the solution to Antimicrobial Resistance (AMR)?
Molecular De-extinction proposes a new way to combat AMR.
With the need for urgent measures to address this great threat, AMR, which is a trend and a major concern in the field of medicine resulting in infections causing approximately 1.27 million deaths annually worldwide, and projections indicating a potential 10 million annual fatalities by 2050 in the absence of effective new drugs, researchers have discovered that by separating peptides with antimicrobial activities from our ancestors we can have a new framework for drug discovery against AMR giving rise to the field of Molecular De-extinction.
With this, we can close the chapter on what Molecular De-extinction entails but let's dive a little deeper into the "What", "Why" and "How" of Molecular De-extinction.
What is Molecular De-extinction?
From the words Molecular and De-extinction, Molecular De-extinction is the process of bringing back/regenerating the molecules of our ancestors from the fossils found.
Why Molecular De-extinction?
It's obvious that though our ancestors lived in far less hygienic conditions they seemed to have been able to survive just fine, this goes to tell us that there might be molecules that proffered them some level of protection from the infection by these micro-organisms, so if we can extract and purify these molecules they can help the modern man gain some level of protection too. The above is the rationale behind Molecular De-extinction as a framework for drug discovery.
How does it work?: APEX and EPs
1. APEX: Antibiotic Peptide de-Extinction. This is a deep learning (DL) model that employs a multitask learning architecture to predict whether EPs(Encrypted Peptides) have antimicrobial activity. Basically, like genomes, humans have proteomes, which is our total protein build-up. So this model runs through the dataset for our(our ancestors and the modern man) proteomes to extract hidden(encrypted) peptides with antimicrobial activities with the aid of the dataset fed to it.
2. EPs: Encrypted Peptides(EPs) are fragments within a protein sequence that possess antimicrobial properties. They have been classified into Encrypted Peptides (AEPs) and Modern Encrypted Peptides (MEPs), with AEPs representing Peptides seen only in our extinct ancestors and MEPs for those seen in our ancestors and modern man. The different classes also went on to show different amino acid compositions and different physicochemical properties.
Researchers found out that the AEPs had greater cell membrane depolarizing activity than the MEPs and other known Antimicrobial Peptides (AMPs) like Polymyxin B, suggesting a new framework for tackling AMR. It was hypothesized that this greater cell membrane depolarizing activity might be due to the amino acid differences in the different classes of peptides. Some AEPs discovered amongst many include Anomalopterin-1 from Anomalopteryx didiformis, Mylodonin from Mylodon darwinii, and Hesperelin-1 from Hesperelaea palmeri.
Conclusion:
With the invention of Molecular De-extinction, using ancient molecules to solve present-day challenges researchers might have just found the solution to the urgent challenge of AMR. As more research is carried out this field will be explored more and its potential usefulness in other fields beyond Clinical Medicine will be discovered and enhanced.
Reference
Wan, F., Torres, M. D., Peng, J., & de la Fuente-Nunez, C. (2023). Molecular De-Extinction of Antibiotics Enabled by Deep Learning. https://doi.org/10.1101/2023.10.01.560353
Written by Ayebamiebi Yousuo from MEDILOQUY