Antimicrobial peptides fight viral diseases but a structural flaw makes them difficult to use as drugs. A deft molecular fix could create synthetic “peptoids” to cure diseases.
Among the powerful biochemicals of the human immune system, peptides are one of the best.
Most commonly found in the places where microbes love to take root – mucous membranes of the eye, mouth, nose, and lungs – they’re known to kill all sorts of tiny invaders, such as viruses, bacteria, and fungi.
Given their power, one might think peptides would represent promising drug treatments, perhaps even a cure, for many infectious diseases. But, alas, they are fundamentally flawed: They are vulnerable to a myriad of enzymes whose job is to rapidly break them down in a way that robs them of their therapeutic properties.
但是，正如巴伦（Barron）在期刊上所描述的那样Pharmaceuticals, she and a team of collaborators have now created peptide-like molecules – which she calls “peptoids” – that could circumvent peptides’ shortcomings and turn these new molecules into the basis for an emerging category of antiviral drugs that could treat everything from herpes and COVID-19 to the common cold. Although Barron cautions that years of development and testing remain before these peptoid-based drugs will make it to market, results to date are extremely encouraging.
A better backbone
肽是一种被称为“仿生学”的生化类型 - 模仿生物分子的行为，但具有某些关键优势。
In their study, Barron and team chose to focus on the herpes virus, which is most notable for causing cold sores around the mouth, sexually transmitted infections and even certain forms of blindness. If contracted later in life, herpes can be particularly devastating to its host. Herpes virus brain infections also are associated with Alzheimer’s disease, an active area of research.
The team reviewed a number of prospective peptoids, beginning with a library of 120 molecular structures – which were at that point just chemical symbols on a page. Based on preliminary experiments, they narrowed these to 10 promising candidates, which her team synthesized. Barron then worked with professor Gill Diamond (University of Louisville) to test her newly minted molecules not just for their effectiveness against the herpes virus, but also for their effect on healthy human cells from the exterior surface of the mouth – known as the oral epithelium.
As expected, some of the peptoids showed no effect against the virus. Others were active, but harmful to healthy host cells. But a precious handful of five peptoids proved worthy of additional study. In the end, two hit the sweet spot – defanging the herpes virus while not harming epithelial cells. One of the candidates, in fact, showed “complete” effectiveness against the virus, and that has Barron excited about the possibilities for treating herpes and, perhaps, beyond.
Barron has since sent samples of peptoids to infectious disease labs around the world asking them to test these new structures against a host of virulent strains, most notably the SARS-CoV-2 virus that causes COVID-19, but also more familiar viruses like influenza and rhinovirus, the culprit behind the common cold.
巴伦说：“我合作者的早期报道非常令人鼓舞。”“因为我们的肽模仿了一种非常特定的人类广谱抗病毒肽-Cathelicidin LL-37 - 我们对它们起作用并不感到惊讶，但仍然非常高兴看到这些结果来自世界各地。”
Reference: “Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids” by Gill Diamond, Natalia Molchanova, Claudine Herlan, John A. Fortkort, Jennifer S. Lin, Erika Figgins, Nathen Bopp, Lisa K. Ryan, Donghoon Chung, Robert Scott Adcock, Michael Sherman and Annelise E. Barron, 31 March 2021,Pharmaceuticals。