The heparin factor was known in August when Yanmei Hu’s doctoral thesis was posted.
We also characterized the broad-spectrum antiviral activity of lactoferrin (LF) and brilacidin against multiple common human coronaviruses including HCoV-OC43, HCoV-NL63, and HCoV-229E as well as SARS-CoV-2 pseudovirus and their mechanism of action were elucidated. Both LF and brilacidin were found to bind to Heparan sulfate proteoglycan (HSPGs) on the host cell surface, thereby preventing viral attachment to the host cells, as evidenced by 1) drug time-of-addition experiment suggests that both LF and brilacidin exerts antiviral activity at the attachment stage; 2) LF and brilacidin inhibits viral attachment and the inhibition was diminished in the presence of heparin; 3) heparin decreased the potency of LF and brilacidin in cell culture. These studies support the translational potential of LF and brilacidin as broad-spectrum antivirals for coronaviruses including SARS-CoV-2.