Drugs that Inhibit TMEM16 Block COVID-19 Virus

April 7, 2021. Drugs that inhibit TMEM16proteins block SARS-CoV-2 spike protein-induced syncytia formation in the lung leading to lymphocyte depletion and COVID-19 disease pathogenesis. Niclosamide was reported in 2020 by several laboratories as a potent inhibitor of SARS-CoV-2 virus replication. In these recent findings from L. Braga et al.(Nature, doi: 10.1038/s41586-021-03491-6, 2021) and Z. Zhang et al. (Cell Death & Differentiation, doi: 10.1038/s41418-021-00782-3, 2021) TMEM16 proteins were found to regulate virus-induced syncytia formation in alveolar epithelial cells resulting in lymphocyte engulfment and depletion - a disastrous unity leading to disease progression and death (L. Lin et al., Cell Death & Differentiation, doi: 10.1038/s41418-021-00795-y, 2021). Braga et al. (2021) reported niclosamide was a potent inhibitor of TMEM16-mediated syncytia formation and suggest inhibitors of this family of ion channels may also show benefits in blocking inflammatory complications of COVID-19. We are pleased that our earlier report in Frontiers in Pharmacology (2019) and those from our colleague Karl Kunzelmann at the University of Regensburg that niclosamide is an inhibitor of TMEM16 proteins provided insights to motivate these new studies.