Research
Understanding and inhibiting Nsp1, a nonstructural protein in SARS-CoV-2
The SARS-CoV-2 virus, responsible for the ongoing global pandemic, has infected over 774 million people, causing more than 7.03 million deaths worldwide as of March 2024. Upon cell entry, the virus's positive single-stranded RNA genome undergoes translation, producing 29 proteins. The initial long open reading frame yields a polyprotein auto-proteolyzed into 16 nonstructural proteins (Nsps), with Nsp1 contributing to host immune response suppression by selectively inhibiting host protein translation. Cryo-EM studies reveal that Nsp1, particularly residues 148-180, adopts a helix-turn-helix structure upon binding to the 40S ribosome, blocking the mRNA entry tunnel. At 1μM concentration, Nsp1 inhibits in vitro host protein translation efficiency by over 90%. The intrinsically disordered C-terminal (CT) region, residues 148-180, poses challenges for traditional drug discovery methods.
My research is dedicated to uncovering the structural dynamics of the disordered C-terminal region and identifying metal interactions within this domain. I have demonstrated that aquo copper(II) binds to histidine 165 in a synthetic 33-residue C-terminal peptide of Nsp1. My ongoing studies aim to elucidate the impact of copper binding on the full-length Nsp1 protein and its mutant derivatives.
Throughout this project, I have honed a diverse set of skills, including protein expression in bacteria, protein purification, and characterization techniques (SDS-PAGE, mass spectrometry, and crystallography). Additionally, I am proficient in W161 fluorescence, Time Resolved Förster resonance energy transfer (FRET) spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, circular dichroism, and in vitro assays.
Summer Research Experiences
Merck Future Talent Program Intern in Discovery Biologics
I have investigated the role of glycosylation in the function and folding of a pharmaceutically relevant protein by designing various deglycosylated and glycosylated mutants. My work involved the expression, purification, and characterization of these protein constructs. I tested the constructs using ELISA assays and a range of in vitro functional assays to assess their properties and behavior.
Summer 2023, Merck Research Laboratories, South San Fransisco
For students interested in applying to this internship visit the following:
Undergraduate Researcher with Dr. Valentine Vullev
I synthesized biomimetic molecular electrets incorporating non-native amino acid residues and characterized various charge transfer organic compounds using advanced techniques such as UV-Vis spectroscopy, fluorescence spectroscopy, and transient absorption spectroscopy. See Publications for work done on these projects.
June 2017-June 2020, University of California Riverside, Riverside
Funding for my research from 2018-2020 was provided by the NIH through MARC U Star Program. For students at UCR interested in applying please visit the following:
WAVE Fellow with Dr. Harry Gray
I synthesized and purified meso-substituted corroles and characterized their photophysical properties using UV-Vis spectroscopy. Additionally, I analyzed these corroles for their potential applications in cancer theranostics.
June 2019- August 2019, California Institute of Technology, Pasadena
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DAAD RISE Fellow with Dr. Jens Pietsch
I synthesized and purified cathepsin B inhibitors for cancer treatment and tumor radiolabeling. These inhibitors were characterized and tested using relevant assays. See Publications for work done on these projects.
June 2018-August 2018, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany
For students interested in applying to this program visit: