A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Xia, Shuai; Yan, Lei; Xu, Wei; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Tseng, Chien-Te K.; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu

The existence of SARS-like CoV (SL-CoV) and MERS-like CoV (ML-CoV) also pose great threats to public health worldwide. Recent studies identified some types of SL-CoV, such as SL-WIV1-CoV and SL-SHC014-CoV, whose spike (S) proteins highly resemble those of SARS-CoV. These SL-CoVs could use the same SARS-CoV receptor, i.e., angiotensin-converting enzyme-2 (ACE2), to directly enter permissive human cells without need for adaptation (9) (10) (11) . In addition, the ML-CoV, Tylonycteris bat CoV HKU4, was shown to recognize the MERS-CoV receptor CD26 and infect human cells either after introduction of two single mutations (S746R and N762A) into its S protein or with the help of exogenous protease (12, 13) . From a historical perspective, zoonotic CoVs harbor a strong ability to cross species barriers to infect humans rapidly and unpredictably, as illustrated by newly emerging HCoVs (2, 14) . Thus, developing a specific drug that only targets a single HCoV would be ineffective against newly emerging HCoVs (9) (10) (11) . Since no broad-spectrum anti-HCoV drug is currently available for clinical use, it is incumbent to search for a common or conserved target site based on existing HCoVs.