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Updated: Aug 6, 2026
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Procedures for the Identification of SARS-CoV-2 Entry Inhibitors as Potential Antivirals using MLV-Based Pseudoviruses
Published on: February 27, 2026
Identification of a Potent Pan-Coronaviral Main Protease Inhibitor
Pu Chen1,2, Ulrike Strunk2,3, Elena Arutyunova1,2
1Department of Biochemistry, University of Alberta, Edmonton, T6G 2H7 AB, Canada.
Journal of Medicinal Chemistry
|July 16, 2026
Summary
A new broad-spectrum antiviral, AVI8122, effectively inhibits multiple coronaviruses, including SARS-CoV-2 and its variants. This compound shows promise for pandemic preparedness against future zoonotic threats.
Area of Science:
- Virology
- Drug Discovery
- Pandemic Preparedness
Background:
- The emergence of zoonotic coronaviruses like SARS-CoV-2 highlights the need for broad-spectrum antiviral agents.
- Current antiviral strategies often lack efficacy against a wide range of coronaviruses.
Purpose of the Study:
- To identify and characterize a novel covalent pan-coronaviral inhibitor.
- To evaluate the potential of AVI8122 as a therapeutic agent for future coronavirus outbreaks.
Main Methods:
- Biochemical assays to assess Mpro inhibition across different coronavirus genera.
- In vitro cell-based assays to evaluate viral replication inhibition.
- In vivo studies in mouse models to assess therapeutic efficacy and pharmacokinetics.
Main Results:
- AVI8122 demonstrated low nanomolar potency against 19 Mpro enzymes from alpha, beta, gamma, and delta coronaviruses.
- The compound effectively inhibited SARS-CoV-2 replication, including variants of concern, in cellulo.
- AVI8122 showed dose-dependent protection against lethal SARS-CoV-2 infection in mouse models with favorable pharmacokinetics.
Conclusions:
- AVI8122 is a potent covalent pan-coronaviral inhibitor with broad-spectrum activity.
- AVI8122 represents a promising early lead compound for developing antivirals against emerging coronavirus threats.
- The findings support AVI8122's potential role in global pandemic preparedness strategies.
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