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SLAS Discov ; 25(10): 1171-1173, 2020 12.
Article in English | MEDLINE | ID: covidwho-545549

ABSTRACT

The global pandemic caused by the SARS-CoV-2 infection is a health emergency that needs to be addressed immediately. The international scientific community, following World Health Organization (WHO) indications, launched different trials for testing drugs putatively able to block the SARS-CoV-2 infection or treat the COVID-19 disease symptoms. In parallel, studies devoted to a better understanding of SARS-CoV-2 biology are in the course for designing an effective vaccine. One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer. As a serendipity occurrence, nimesulide was shown to abolish the transport function of B0AT1. Here we suggest including nimesulide in the list of drugs to be tested for the identification of co-adjuvants in the treatment of COVID-19.


Subject(s)
Amino Acid Transport Systems, Neutral/metabolism , Antiviral Agents/pharmacology , SARS-CoV-2/pathogenicity , Sulfonamides/pharmacology , Amino Acid Transport Systems, Neutral/chemistry , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Drug Repositioning , Host-Pathogen Interactions/drug effects , Humans , Serine Endopeptidases/metabolism , COVID-19 Drug Treatment
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