Exploring Nicotinamidase Inhibitors as a Potential Treatment for Malaria

Authors

Rasajna Madhusudhana, Virginia Commonwealth University

Original Publication Date

2025

Document Type

Presentation

Comments

First place winner of the 11th Annual VCU 3MT® Competition, held on October 3, 2025

Abstract

Malaria kills over half a million people each year, and growing resistance to current treatments threatens global health progress. Rasajna Madhusudhana’s research targets a key enzyme in the malaria parasite, Plasmodium falciparum nicotinamidase (PFNIC), which is essential for producing NAD—a molecule vital for the parasite’s survival. Unlike human cells, the parasite relies on a single pathway for NAD synthesis, making PFNIC a vulnerable target. By blocking this enzyme, Madhusudhana’s team stopped parasite growth in red blood cells and identified 150 promising inhibitor candidates through virtual screening. Their work paves the way for new antimalarial drugs that could overcome resistance and save lives.

Transcription

Next, we have Rasajna Madhusudhana, Exploring Nicotinamidase Inhibitors as a Potential Treatment for Malaria. They're in the School of Pharmacy, and their advisor is Dr. Yana Cen. Mosquitoes that carry the deadly malarial parasite claim over half a million lives every year, a large number of which are young children from Africa and Southeast Asian countries. In fact, one in every three newborns in Africa are infected. This is really heartbreaking, but what's worse is that these numbers have actually been increasing over the last couple years. In the early 2000s, we thought we were winning our fight against malaria with our hero drug, artemisinin. But steadily, the malarial parasite has been developing resistance and fighting back, which means we may soon see a very deadly comeback of malaria. So what do we do when our best weapons fail us? One, we try to find new weaknesses with our enemy. And two, we try to build stronger weapons to fight. That's exactly what we are trying to do with our research. We found that the malarial parasite's weakness lies in how it makes NAD. Think of NAD as this battery molecule that fuels all the important biochemical processes in a cell. Metabolism, growth, repair, basically everything that's essential for the parasites. survival. NAD is equally important to us. But the catch is, our cells can make NAD in several different ways. But the parasite has just one option. When the parasite infects our red blood cells, it steals NAM, the primary precursor of NAD, from our blood cells and processes it using this enzyme called PFNIC to then make NAD. So we asked ourselves, what if we block this PFNIC? So we went ahead and treated the parasites growing in red blood cells, which is the blue spots you see there, with the PFNIC inhibitor. And they stopped growing. And when we supplemented it with the missing nutrient, they bounced back. This confirmed to us that PFNIC is indeed a very important switch. And turning off this one switch can lead to a cascade of negative effects on the parasites' survival, growth, and infectivity. As the next stage of our work, we sought to find better, stronger inhibitors of PFNIC. So far, we have virtually screened about 33,000 small molecules and narrowed down to 150 promising candidates. In the future, we will be testing them in various levels with each step getting closer to a new anti-malarial agent. This new treatment can be used both independently and along with existing drugs to outsmart resistance. We are very confident that we are developing a strong weapon against malaria. And one day, these PFNIC inhibitors will be able to attack the malarial parasite right in its Achilles heel. Thank you.

Rights

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