Signal Transduction and Targeted Therapy, 26 August, 2021, DOI：https://doi.org/10.1038/s41392-021-00737-7

Repurposing of a clinically used anti-HPV agent to prevent and treat SARS-CoV-2 infection as an intranasal formulation

Chen Hua, Qinhai Ma, Yun Zhu, Shuai Xia, Zezhong Liu, Lin Li, Lu Lu, Nanshan Zhong, Shuwen Liu, Zifeng Yang & Shibo Jiang

Abstract

Fan et al. have shown that whey protein, such as that found in human, bovine, and goat milk, could effectively inhibit SARS-CoV-2 infection, but they did not identify the components in whey protein having this activity. Since β-lactoglobulin (β-LG) is the main component of whey protein, we herein tested the anti-SARS-CoV-2 activity of β-LG and 3-hydroxyphthalic anhydride (3HP)-modified β-LG (3HP-β-LG), an active component in anti-human papillomavirus (HPV) biological dressing (JB01-BD) that has been used in clinics since 2013 to block cervical infection of HPV. Surprisingly, β-LG could not inhibit SARS-CoV-2 pseudovirus (PsV) infection in 293T/ACE2 cells at the concentration as high as 40μM. In contrast, 3HP-β-LG, like Griffithsin (GRFT) that targets the SARS-CoV-2 S-RBD and EK1 that targets the SARS-CoV-2 S-HR1, was very effective in inhibiting SARS-CoV-2 PsV infection with a half-maximal inhibitory concentration (IC₅₀) of 0.84±0.29μM (Fig. 1a). Similarly, 3HP-β-LG could also inhibit SARS-CoV-2 PsV infection in Calu-3 cells, a lung epithelial cell line (Supplementary Fig. S1). We found that 3HP-β-LG could also inhibit authentic SARS-CoV-2 infection in Vero-E6 cells with an IC₅₀ of 2.31μM, while, again, β-LG had no inhibitory activity at the concentration up to 40μM (Fig. 1b).

Article link：https://www.nature.com/articles/s41392-021-00737-7