Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the virus causing the COVID-19 pandemic, continues to spread worldwide at an unprecedented rate. SARS-CoV-2 infects the nasal epithelium, lung parenchyma, gut enterocytes, and endothelial cells. Individuals with pre-existing conditions have a higher risk for developing a more severe COVID-19 associated with a higher rate of mortality. Severe cases of COVID-19 can rapidly progress to acute respiratory distress syndrome, with cardiac injury, kidney injury, and multiple organ dysfunction. While the understanding of SARS-CoV-2 infection and COVID-19-associated pathophysiology is increasing, there is urgent need to develop effective antiviral drugs for COVID-19, which could potentially be used in combinations. We recently discovered that our potent heparanase inhibitor, sulfated disaccharide-functionalized polymer, is a potent competitor of the interaction of SARS-CoV-2 spike with heparin. In addition, when the wild-type SARS-CoV-2 was pre-incubated with this glycopolymer and subsequently applied onto Vero-E6 cells for infection, significant inhibition of SARS-CoV-2 replication and release was noted by quantitative RT-PCR analyses of the viral genomic RNA, which represents the mature progeny virus and the viral sub-genomic mRNA in the infected cells. This most promising SARS-CoV-2 inhibitor is currently examined, using a unique <i>ex vivo</i> model system, to specifically study viral infection, replication and spread in native integral human respiratory tract tissues of the nasal mucosa and lung.

Discovery of sulfated glycopolymers for targeting heparanase in cancer and SARS-CoV-2 infection

ACS Spring Meeting 2021

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