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submitted on 02.09.2020 and posted on 03.09.2020by Yangyang Cheng, Anh-Tuan Pham, Takehiro Kato, Bumhee Lim, Dimitri Moreau, Javier López-Andarias, Lili Zong, Naomi Sakai, Stefan Matile
Viral entry into cells can involve thiol-disulfide exchange with exofacial thiols on cell surfaces. The importance of thiol-mediated uptake for viral entry and beyond is poorly understood because efficient inhibitors do not exist. Here we use fluorescent cyclic oligochalcogenides that enter cells by thiol-mediated uptake to systematically screen for inhibitors, including epidithiodiketopiperazines, benzopolysulfanes, disulfide-bridged g-turned peptides, heteroaromatic sulfones and cyclic thiosulfonates, thiosulfinates and disulfides. Different activities found with different reporters reveal thiol-mediated uptake as a complex multitarget process. Initial tests with pseudo-lentivectors expressing SARS-CoV-2 spike protein do not exclude potential for the development of new antivirals