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Updated: Jun 23, 2026

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds
Published on: October 29, 2015
Development of Orally Bioavailable Octahydroindole-Based Peptidomimetic Derivative as a Broad-Spectrum Inhibitor
Shulei Hu1,2, Yumin Zhang3, Chenchen Wang2,4,5
1Department of Medicinal Chemistry, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing 211198, China.
Abstract:
A series of novel Mpro inhibitors was designed and synthesized to combat the coronavirus, such as HCoV-OC43 and SARS-CoV-2, and several compounds showed comparable antiviral activity to nirmatrelvir. Among them, an octahydroindole-based peptidomimetic covalent inhibitor 28f showed strong inhibitory activity against Mpros and exhibited broad-spectrum anticoronavirus activity with EC50 values ranging from 0.027 to 4.41 μM. Besides, this compound displayed potent antiviral activity against EV71. Compared to FB2001, 28f displayed better pharmacokinetic properties, and the value of oral bioavailability in CD-1 mice and Beagle dogs was improved to 10.4 and 10.2%, respectively. In addition, oral treatment with 28f could significantly reduce the viral loads of HCoV-OC43 in mice, and compound 28f could also effectively reduce lung viral loads in a K18-hACE2 transgenic mouse model without ritonavir. Taken together, compound 28f is a promising orally bioavailable broad-spectrum antiviral drug candidate that deserves further research.
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