| Literature DB >> 36175661 |
Chang-Ki Oh1, Tomohiro Nakamura1, Nathan Beutler2, Xu Zhang1, Juan Piña-Crespo1, Maria Talantova1, Swagata Ghatak1, Dorit Trudler1, Lauren N Carnevale1, Scott R McKercher1, Malina A Bakowski3, Jolene K Diedrich1, Amanda J Roberts4, Ashley K Woods3, Victor Chi3, Anil K Gupta3, Mia A Rosenfeld5, Fiona L Kearns5, Lorenzo Casalino5, Namir Shaabani2, Hejun Liu6, Ian A Wilson6, Rommie E Amaro5, Dennis R Burton2, John R Yates1, Cyrus Becker7, Thomas F Rogers2,8, Arnab K Chatterjee3, Stuart A Lipton9,10.
Abstract
Prevention of infection and propagation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a high priority in the Coronavirus Disease 2019 (COVID-19) pandemic. Here we describe S-nitrosylation of multiple proteins involved in SARS-CoV-2 infection, including angiotensin-converting enzyme 2 (ACE2), the receptor for viral entry. This reaction prevents binding of ACE2 to the SARS-CoV-2 spike protein, thereby inhibiting viral entry, infectivity and cytotoxicity. Aminoadamantane compounds also inhibit coronavirus ion channels formed by envelope (E) protein. Accordingly, we developed dual-mechanism aminoadamantane nitrate compounds that inhibit viral entry and, thus, the spread of infection by S-nitrosylating ACE2 via targeted delivery of the drug after E protein channel blockade. These non-toxic compounds are active in vitro and in vivo in the Syrian hamster COVID-19 model and, thus, provide a novel avenue to pursue therapy.Entities:
Year: 2022 PMID： 36175661 DOI： 10.1038/s41589-022-01149-6
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 16.174