Research in the Chang Lab
Current Research Interests
Investigation of broad-spectrum antivirals against human coronaviruses
Over the past two decades, coronaviruses, a group of single-stranded positive-strand RNA viruses, have triggered three significant outbreaks. These include Middle East respiratory syndrome-related coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergence of SARS-CoV 2 in December 2019 led to 776 million infections and 7 million fatalities worldwide by October 2024. Each outbreak was characterized by substantial illness and death rates, highlighting the critical need for effective antiviral treatments against human coronavirus. These outbreaks have underscored the importance of developing broad-spectrum antiviral therapies capable of targeting multiple coronaviruses. My group has been focusing on identifying potential drug targets and exploring novel compounds that can inhibit coronavirus replication or modulate the host immune response to infection. To achieve this goal, we recently developed a robust human cell model expressing multiple viral receptors and successfully demonstrated its susceptibility to SARS-CoV-2, MERS-CoV, and seasonal coronaviruses such as OC43, 229E, and NL63 (See Schematic). Using this cell model, we screened a drug repurposing library and identified several small molecules demonstrating broad-spectrum activity against both the omicron variant JN.1 and MERS-CoV from 1,842 compounds, offering a promising direction for developing new therapies.
Selected Publications
Meyer C, Garcia A, Miller M, Huggins D, Myers R, Hoffmann HH, Ashbrook A, Jannath S, Liverton N, Kargman S, Zimmerman M, Nelson A, Sharma V, Cangialosi J, Penalva-Lopez S, Ramos-Espiritu L, Menezes MR, Larson C, Nitsche J, Alwaseem H, Molina H, Steinbacher S, Glickman JF, Perlin D, Rice C, Meinke P, Dolgov E, Alvarez N, Chang CW, Oswal N, Jimenez IG, Rasheed R, Goldgirsh K, Davis J, Ganichkin O, Tuschl T.
Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase.
Nature. 2024.
In Press
Hong SJ, Resnick S, Iketani S, Cha JW, Albert B, Fazekas C, Chang CW, Liu H, Dagan S, Abagyan M, Fajtová P, Culbertson B, Brace B, Reddem E, Forouhar F, Glickman JF, Balkovec J, Stockwell B, Shapiro L, O'Donoghue A, Sabo Y, Freundlich J , Ho D.
A multiplex method for rapidly identifying viral protease inhibitors.
Molecular Systems Biology. 2024.
In Press
Hariharan VN*, Shin M*, Chang CW*, O'Reilly D, Biscans A, Yamada K, Guo Z, Somasundaran M, Tang Q, Monopoli K, Krishnamurthy PM, Devi G, McHugh N, Cooper DA, Echeverria D, Cruz J, Chan IL, Liu P, Lim SY, McConnell J, Singh SP, Hildebrand S, Sousa J, Davis SM, Kennedy Z, Ferguson C, Godinho BMDC, Thillier Y, Caiazzi J, Ly S, Muhuri M, Kelly K, Humphries F, Cousineau A, Parsi KM, Li Q, Wang Y, Maehr R, Gao G, Korkin D, McDougall WM, Finberg RW, Fitzgerald KA, Wang JP, Watts JK, Khvorova A.
Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection.
Proc Natl Acad Sci. 2023
*co-first author
PMID: 36893269
Chang CW, Parsi KM, Somasundaran M, Vanderleeden E, Liu P, Cruz J, Cousineau A, Finberg RW, Kurt-Jones EA.
A Newly Engineered A549 Cell Line Expressing ACE2 and TMPRSS2 Is Highly Permissive to SARS-CoV-2, Including the Delta and Omicron Variants.
Viruses. 2022
PMID: 35891350
Chang CW, Wakeland AK, Parast MM.
Trophoblast lineage specification, differentiation and their regulation by oxygen tension.
J Endocrinol. 2018
PMID: 29259074