Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition
Ju‐Ri Sim, Dong Hoon Shin, Pil‐Gu Park, Sohyeon Park, Joon‐Yong Bae, Youngchae Lee, Dha-Yei Kang, Ye Jin Kim, Sowon Aum, Shin Hye Noh, Su Jin Hwang, Hye‐Ran Cha, Cheong Bi Kim, Si Hwan Ko, Sunghoon Park, Dongkyu Jeon, Sungwoo Cho, Gee Eun Lee, Jeonghun Kim, Young-hye Moon, Jae‐Ouk Kim, Jae Sung Nam, Chang‐Hoon Kim, Sungmin Moon, Youn Wook Chung, Man‐Seong Park, Ji-Hwan Ryu, W. Namkung, Jae Myun Lee, Min Goo Lee
Abstract
elevation and ANO6-dependent phosphatidylserine externalization in ACE2/TMPRSS2-positive mammalian cells. A high-throughput screening of drug-like chemical libraries identifies three different structural classes of chemicals showing ANO6 inhibitory effects. Among them, A6-001 displays the highest potency and ANO6 selectivity and it inhibits the single-round infection of SARS2-PsV in ACE2/TMPRSS2-positive HEK 293T cells. More importantly, A6-001 strongly inhibits authentic SARS-CoV-2-induced phosphatidylserine scrambling and SARS-CoV-2 viral replications in Vero, Calu-3, and primarily cultured human nasal epithelial cells. These results provide mechanistic insights into the viral entry process and offer a potential target for pharmacological intervention to protect against coronavirus disease 2019 (COVID-19).