Pharmaceuticals (Basel) . Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules

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Pharmaceuticals (Basel)


. 2020 Dec 8;13(12):E447.
doi: 10.3390/ph13120447.
Inhibition of SARS-CoV-2 Entry into Host Cells Using Small Molecules


Kenana Al Adem ¹ , Aya Shanti ¹ , Cesare Stefanini ¹ , Sungmun Lee ^{1 2}



Affiliations

• PMID: 33302344
• DOI: 10.3390/ph13120447

Free article

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a virus belonging to the Coronavirus family, is now known to cause Coronavirus Disease (Covid-19) which was first recognized in December 2019. Covid-19 leads to respiratory illnesses ranging from mild infections to pneumonia and lung failure. Strikingly, within a few months of its first report, Covid-19 has spread worldwide at an exceptionally high speed and it has caused enormous human casualties. As yet, there is no specific treatment for Covid-19. Designing inhibitory drugs that can interfere with the viral entry process constitutes one of the main preventative therapies that could combat SARS-CoV-2 infection at an early stage. In this review, we provide a brief introduction of the main features of coronaviruses, discuss the entering mechanism of SARS-CoV-2 into human host cells and review small molecules that inhibit SARS-CoV-2 entry into host cells. Specifically, we focus on small molecules, identified by experimental validation and/or computational prediction, that target the SARS-CoV-2 spike protein, human angiotensin converting enzyme 2 (ACE2) receptor and the different host cell proteases that activate viral fusion. Given the persistent rise in Covid-19 cases to date, efforts should be directed towards validating the therapeutic effectiveness of these identified small molecule inhibitors.

Keywords: Covid-19; SARS-CoV-2; angiotensin converting enzyme 2; inhibitors; small molecule; spike protein.