The SARS-CoV-2 virus has persisted at pandemic levels for two years and produced devastating effects not only on human health but also on the global economy. It is highly urgent to develop therapeutic strategies to combat current and future variations of the SARS-CoV-2 virus.  Several vaccines have been developed and are widely used, however appear less efficacious for new SARS-CoV-2 variants. Thus, there is an urgent need to develop antiviral agents. Sialidases catalyze the cleavage of sialic acid residues from their component glycans of either glycoprotein or glycolipid. Sialidase is expressed at higher level in the respiratory tract of severe COVID-19 patients and represents an attractive therapeutic target for COVID-19. HCoV-OC43 is a human pathogen that belongs to the same clade of beta-coronaviruses as SARS-CoV-2 and can be studied in an attempt to discover broad spectrum anti-coronavirus drugs that would be beneficial against SARS-CoV-2 and future emerging coronaviruses. In our recent study, we synthesized and assessed multiple sialidase inhibitors for antiviral activity against HCoV-OC43 in vitro. The tested sialidase inhibitors significantly repressed HCoV-OC43 replication. In addition, a high-throughput screen (HTS) assay showed that these sialidase inhibitors have similar effects on the replication of SARS-CoV-2. Our results indicate that sialidase inhibitors may serve as drug candidates for developing a novel treatment for SARS-CoV-2 infection.

Synthesis of sialidase inhibitors with different polarities and their anti-Coronavirus replication activities

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