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  • Randy Dang

Expanding our Arsenal in Humanity's War Against Pathogens

Antibiotics are used to treat bacterial infections. Vaccines help protect us from viral infections. But what happens when antibiotics lose their effectiveness, or if a vaccine for a particular virus just isn’t available? Clearly, alternative forms of treatment are necessary, especially because so many bacteria are now resistant to common antibiotics. A main focus of Professor Krishna Kumar’s laboratory is developing alternative ways to defend ourselves against pathogens, adding more effective and accessible methods to our arsenal.


Background


Professor Krishna Kumar of the Tufts University Chemistry Department has been a professor at Tufts for 22 years. He grew up in India and Thailand and got his B.S. at St. Stephen’s College in Delhi, India. Growing up, he has considered many careers including professional sports, but ultimately, chemistry won out because of how central it is to the biological and medical setting. He found it particularly fascinating that many fields that he wished to do work in, such as drug discovery and studying the origin of life, can be brought to the molecular level.


After graduating from St. Stephen’s College, Kumar went on to get his Ph.D. at Brown University and completed his postdoctoral training in 1998 at Scripps Research Institute.


Antibiotics


Almost a century ago, Alexander Fleming, upon close examination of some mold that entered an uncovered plate of bacteria, found that the mold killed the bacteria. This discovery was huge yet completely accidental! Penicillin, the product produced by the mold, became the first antibiotic, and it was widely used to treat bacterial infections. As a then-miracle drug, it killed almost all bacteria that it came in contact with.


However, there was one problem: a select few bacteria were resistant to the antibiotic, so they were not killed by the penicillin. As more bacteria without resistance were killed, the resistance became more common. To partially counteract this, other antibiotics were developed, but over time, resistance to them also became more prevalent. As Kumar puts it, “We are on the verge of the last resort for antibiotics.” Once those antibiotics become ineffective, we will return “to a pre-penicillin era.” Thus, we need something different in our arsenal, something that today’s bacteria would not have much of a resistance to.


Currently, the Kumar Lab is in the early stages of developing a new form of antibiotic that focuses on the selection of peptides. Although this is a conceptual idea that has not yet been implemented, it is promising. As a novel way of killing bacteria, very few would have resistance. Once it is implemented, it would take a lot longer before bacterial resistance to this novel treatment becomes common.


The Current Pandemic


Due to the significant effects that COVID-19 has had on our world and the lack of available options prior to the release of the vaccine, it is more important than ever to have a multifaceted arsenal of protections both to help with this current pandemic and

to prevent future pandemics.


In June of 2020, Kumar published an article titled “Exploiting Existing Molecular Scaffolds for Long-Term COVID Treatment.” Since the strategy of figuring out ways to treat COVID-19 tended to focus on either using existing treatments or developing vaccines, the purpose of this article was to summarize the COVID-19 viral life cycle (similar to the life cycle of similar coronaviruses) and inspire ideas for novel treatments. Especially due to uncertainties in the timeline of vaccine development and rollout at the time, taking multiple approaches to tackling the current pandemic was beneficial.


Figure above provides a summary of the SARS-CoV-2

(the virus that causes COVID-19) life cycle


Ideas for novel treatments involve disrupting SARS-CoV-2 at any stage in its life cycle, including preventing entry of the virus into the cell, preventing replication of the viral genetic material, interfering with the processing of proteins, and interfering with reassembly of the virus. Although remdesivir is a drug that interferes with the replicating of genetic material, it is far from becoming an effective treatment. However, the current mRNA COVID-19 vaccines interfere with the SARS-CoV-2 life cycle at the protein stage. Overall, in writing this publication, Kumar hopes to encourage the scientific community to think of broader ways to tackle the current COVID-19 pandemic.


These different approaches for treating viruses are especially important because vaccines are not always feasible. For example, we do not currently have a vaccine for HIV, but that’s okay because we have developed other methods of treating people with HIV and HIV has been studied for a long time. Unfortunately, however, COVID-19 is different because of how recently SARS-CoV-2 came to be. Nevertheless, developments could have been made in advance of this pandemic that would have averted COVID-19’s most drastic effect on our lives.


As Kumar describes, “We never got a handle on SARS-CoV-1.” If we did, SARS-CoV-2 would not be as much of an issue. We must now ask: Even though a vaccine for SARS-CoV-2 has been developed, what would happen if SARS-CoV-3 emerges? Considering multiple ways to treat COVID-19 by developing ways to disrupt the SARS-CoV-2 life cycle can not only increase our options in dealing with the current pandemic, but also help us prepare better for a potential SARS-CoV-3 virus and avoid any drastic effects that it may impose.


Ideas for novel treatments involve disrupting SARS-CoV-2 at any stage in its life cycle, including preventing entry of the virus into the cell, preventing replication of the viral genetic material, interfering with the processing of proteins, and interfering with reassembly of the virus. Although remdesivir is a drug that interferes with the replicating of genetic material, it is far from becoming an effective treatment. However, the current mRNA COVID-19 vaccines interfere with the SARS-CoV-2 life cycle at the protein stage. Overall, in writing this publication, Kumar hopes to encourage the scientific community to think of broader ways to tackle the current COVID-19 pandemic.


These different approaches for treating viruses are especially important because vaccines are not always feasible. For example, we do not currently have a vaccine for HIV, but that’s okay because we have developed other methods of treating people with HIV and HIV has been studied for a long time. Unfortunately, however, COVID-19 is different because of how recently SARS-CoV-2 came to be. Nevertheless, developments could have been made in advance of this pandemic that would have averted COVID-19’s most drastic effect on our lives.


As Kumar describes, “We never got a handle on SARS-CoV-1.” If we did, SARS-CoV-2 would not be as much of an issue. We must now ask: Even though a vaccine for SARS-CoV-2 has been developed, what would happen if SARS-CoV-3 emerges? Considering multiple ways to treat COVID-19 by developing ways to disrupt the SARS-CoV-2 life cycle can not only increase our options in dealing with the current pandemic, but also help us prepare better for a potential SARS-CoV-3 virus and avoid any drastic effects that it may impose.


The Silent Pandemic


In addition to the current pandemic, Professor Kumar believes that there is another “silent pandemic.” Over the years, cases of obesity, diabetes, and Parkinson’s Disease have increased substantially, and more and more people require treatments for those conditions. This “silent pandemic” even relates to the current COVID-19 pandemic, as obesity has proved to be a significant risk factor for strong symptoms from COVID-19. Unfortunately, the drugs treating these conditions are often very expensive, making them largely inaccessible to the public.


To counteract this, Kumar and his team are trying to develop alternative pathways for the formation of those treatments that are less costly. This would lower the cost of expensive medications and ultimately make treatments more accessible. Thus, issues resulting from the increases in obesity, diabetes, and Parkinson’s Disease would decrease drastically.


It is important to recognize that there is no common solution for all pathogens. Different pathogens operate differently, and the most appropriate treatment often varies from pathogen to pathogen. Additionally, treatments that are effective today may lose their effectiveness a century later, as demonstrated by penicillin’s decline in effectiveness. The Kumar Lab is thinking of broader ways to fight pathogens to increase humanity’s defenses in novel ways, and Kumar encourages the scientific community to do so as well. On a more cautious note, we also need to consider potential risks and side effects both on the people receiving the treatment and the world at large. In short, we must increase our arsenal to be as prepared as possible against pathogens while remaining careful not to cause a significant amount of destruction.

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