Open AccessA novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells
Author(s) -
Matthew Mahoney,
Vishnu C. Damalanka,
Michael A. Tartell,
Dong Hee Chung,
André Luiz Lourenço,
Dustin Pwee,
Anne E Mayer Bridwell,
Markus Hoffmann,
Jorine J. L. P. Voss,
Partha Karmakar,
Nurit P. Azouz,
Andrea M. Klingler,
Paul W. Rothlauf,
Cassandra E Thompson,
Melody Lee,
Lidija Klampfer,
Christina L. Stallings,
Marc E. Rothenberg,
Stefan Pöhlmann,
Sean P. J. Whelan,
Anthony J. O’Donoghue,
Charles S. Craik,
James W. Janetka
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2108728118
Subject(s) - tmprss2 , virology , serine protease , ex vivo , proteases , coronavirus , protease , in vivo , virus , cytopathic effect , viral entry , protease inhibitor (pharmacology) , biology , chemistry , viral replication , viral load , enzyme , covid-19 , medicine , biochemistry , disease , pathology , infectious disease (medical specialty) , microbiology and biotechnology , antiretroviral therapy
Significance MM3122 represents an advanced lead candidate for clinical development as a novel antiviral drug for COVID-19. In addition to being novel drugs, these selective TMRSS2 inhibitors can be used as valuable chemical probes to help elucidate mechanisms of viral pathogenesis. Since TMPRSS2 plays a key role as a viral protein processing protease in the pathogenesis of other coronaviruses (SARS-CoV, MERS-CoV) as well as influenza viruses, MM3122 and this class of TMPRSS2 inhibitors hold much promise as new drugs to not only treat SARS-CoV-2 infections but also potentially represent broad-spectrum antivirals.