Development of Mouse Hepatitis Virus Chimeric Reporter Viruses Expressing the 3CLpro Proteases of Human Coronaviruses HKU1 and OC43 Reveals Susceptibility to Inactivation by Natural Inhibitors Baicalin and Baicalein
Elise R. Huffman,
Jared X. Franges,
Jayden M. Doster,
Alexis R. Armstrong,
Yara S. Batista,
Cameron M. Harrison,
Jon D. Brooks,
Morgan N. Thomas,
Butler Student Virology Group,
Sakshi Tomar,
Christopher C. Stobart,
Dia C. Beachboard
Affiliations
Elise R. Huffman
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Jared X. Franges
Department of Biology, DeSales University, Center Valley, PA 18034, USA
Jayden M. Doster
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Alexis R. Armstrong
Department of Biology, DeSales University, Center Valley, PA 18034, USA
Yara S. Batista
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Cameron M. Harrison
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Jon D. Brooks
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Morgan N. Thomas
Department of Biology, DeSales University, Center Valley, PA 18034, USA
Butler Student Virology Group
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Sakshi Tomar
National Cancer Institute, Bethesda, MD 20892, USA
Christopher C. Stobart
Department of Biological Sciences, Butler University, Indianapolis, IN 46208, USA
Dia C. Beachboard
Department of Biology, DeSales University, Center Valley, PA 18034, USA
The recent emergence of SARS-CoV-2 in 2019 has highlighted the necessity of antiviral therapeutics for current and future emerging coronaviruses. Recently, the traditional herbal medicines baicalein, baicalin, and andrographolide have shown inhibition against the main protease of SARS-CoV-2. This provides a promising new direction for COVID-19 therapeutics, but it remains unknown whether these three substances inhibit other human coronaviruses. In this study, we describe the development of novel chimeric mouse hepatitis virus (MHV) reporters that express firefly luciferase (FFL) and the 3CLpro proteases of human coronaviruses HKU1 and OC43. These chimeric viruses were used to determine if the phytochemicals baicalein, baicalin, and andrographolide are inhibitory against human coronavirus strains HKU1 and OC43. Our data show that both baicalein and baicalin exhibit inhibition towards the chimeric MHV strains. However, andrographolide induces cytotoxicity and failed to demonstrate selective toxicity towards the viruses. This study reports the development and use of a safe replicating reporter platform to investigate potential coronavirus 3CLpro inhibitors against common-cold human coronavirus strains HKU1 and OC43.
