The iDPCC is thrilled to spotlight several CEIRR researchers who earned a poster presentation award at the 4th Annual CEIRR Network Meeting (ANM). Our seventh spotlight of this series is Konstantin Andreev, Ph.D., a postdoctoral research associate in the Webby Lab at St. Jude Children’s Research Hospital, part of St. Jude Children’s Research Hospital CEIRR (SJCEIRR). Andreev earned First Place in the H5/Risk Assessment category for his poster titled “A Disconnect Between In Vitro and In Vivo Activity of Influenza Antivirals Against Severe Influenza A(H5N1) Clade 2.3.4.4b Infections.”
Andreev and his colleagues assessed pandemic risks through predicting the effectiveness of FDA-approved antiviral medications against highly pathogenic influenza A(H5N1) viruses that have the potential for zoonotic spillover. The team evaluated in vivo efficacy of neuraminidase inhibitor oseltamivir, cap-dependent endonuclease inhibitor baloxavir acid (baloxavir), nucleoside analogue favipiravir, and M2 ion channel inhibitor amantadine against novel clade 2.3.4.4b viruses. Phenotypic assays showed that currently circulating influenza strains are susceptible to all antivirals at nano- to micromolar concentrations. However, oseltamivir and favipiravir provided limited survival benefits in mice, and amantadine failed to protect from lethality. Baloxavir was the only drug that was able to control severe A(H5N1) infection and protect 80-100% of mice. The discrepancy between in vitro and in vivo results indicate that in vitro assessment of antiviral drugs against emerging influenza clades may not give the full picture, and underscores the importance of animal studies.
Andreev told the iDPCC that his “passion lies less in addressing fundamental scientific questions but rather translating knowledge and discoveries into tangible solutions or innovative products that may benefit humanity.” He believes that “Antivirals play a pivotal role in pandemic preparedness and may serve as first-line countermeasures against emerging strains, when vaccines become unavailable.” Additionally, he credited the CEIRR Program for fostering collaborations, stating “the CEIRR Program brings together leading experts in the field, facilitating the exchange of data, globally collected viral samples, and even opportunities for ‘hands-on’ help.” He highlights that the “coordinated effort is essential for staying ahead of such a fast-moving threat.”
To learn more about Andreev, the iDPCC asked several insightful questions:
1. Who/what inspired you to go into science in general?
A. Although most of my family members were musicians, artists, and entrepreneurs, they had a significant influence on my decision to tie myself to the life sciences, and helped shape my investigative mindset.
2. What is one thing on your bucket list?
A. One of the things on my to-do list is visiting all 195 countries in the world. So far, I barely made it up to 30 and have a lot of space in my passport for more stamps.
3. How have your career interests and plans changed over time?
A. My closer interaction with virology has started at a pretty late stage, when I transited a long way from molecular biophysics of cellular membranes and biological interfaces. The unique properties of surface-active biomaterials (a.k.a. surfactants) forming a natural barrier in the lung’s alveoli sparked the idea of its structure to be interfered by respiratory pathogens. To validate my hypothesis, I have joined the lab of Robert Lamb (1950-2023), a renowned virologist, at Northwestern University. Among many RNA viruses, influenza appealed to be the most thrilling one with its uniquely segmented genome organization, ecology, and adaptive evolution. So eventually, I moved to St. Jude where Richard Webby runs one of the very few CEIRR centers, likely the best spot to end up for my research goals.
4. Do you have advice for other trainees or students wanting to get started in research?
A. Same as for anyone making venture investments: start early, be persistent and patient; let your intellectual capital grow steadily without getting discouraged by occasional steeps and declines.
5. What technique, skill, or knowledge are you the “go to” person for in your lab?
A. I am routinely involved in phenotypic and sequence screening of the viruses we receive from worldwide to ensure they are susceptible to existing antivirals. We have established and optimized a high-throughput assay to assess sensitivity to polymerase inhibitors with a quicker turnaround time.
6. Do you have any hobbies or special interests that you'd like to share?
A. Outside of the lab, I am a motorcycle rider, a clumsy scuba diver, and wine and oysters connoisseur.