Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity.

"The authors declare the following competing financial interest(s): H. Luesch is co-founder of Oceanyx Pharmaceuticals, Inc., which has licensed patents and patent applications related to apratoxins. The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary and Pfizer, outside of the reported work. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work."

"This research was in part supported by the NIH, National Cancer Institute Grant R01CA172310 (to H.L.), and the Debbie and Sylvia DeSantis Chair professorship (H.L.). Work in the Chanda lab was supported in part by the DoD, Grant W81XWH-20-1-0270, and the NIH/NIAID, Grant Fluomics/NOSI U19AI135972 and DHIPC Grant U19AI118610; and NCI Grant P30CA030199-40; as well as generous philanthropic donations from D. Ruch, and S. and J. Blair (to S.K.C.). This research was also partly supported by CRIPT (Center for Research for Influenza Pathogenesis and Transmission), a NIAID supported Center of Excellence for Influenza Research and Response (CEIRR, Contract # 75N93021C00014), by DARPA Grant HR0011-19-2-0020, by supplements to NIAID Grants U19AI142733, U19AI135972 and DoD Grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (Research Grant 2020-215611 (5384)), and anonymous donors to A.G-S. Work in the Stertz and Hale groups was supported by the Swiss National Science Foundation (Grant Numbers 31003A_176170 (to S.St.) and 31003A_182464 (to B.G.H.)) and imaging performed with support of the Center for Microscopy and Image Analysis, University of Zurich. We thank Sonja Fernbach for her support with the immunofluorescence quantifications using CellProfiler. The authors would like to thank Charles M. Rice (The Rockefeller University, NY) for sharing Huh-7.5 cells, Michael S. Diamond (Washington University School of Medicine in St. Louis) for the West Nile virus, Ana Fernandez-Sesma (Icahn School of Medicine at Mount Sinai) for the Dengue virus, Thomas Rogers (University of California, San Diego) for providing HeLa-hACE2 cells, Sam Wilson (University of Glasgow) for providing the A659-ACE2 cells, and Pei-Yong Shi (University of Texas Medical Branch, Galveston) for the SARS-CoV-2 clone. We thank R. Albrecht for support with the BSL-3 facility and procedures at the Icahn School of Medicine at Mount Sinai, New York."