CoVs are single-stranded, positive-sense, enveloped RNA viruses from the Coronaviridae family. The viral life cycle begins with the attachment of a trimeric spike to cells, which is cleaved by furin-like proteases into S1 and S2 subunits. The virus uses S1’s receptor-binding domain for binding to the host cell receptor, angiotensin-converting enzyme 2 .
The study and findings In the present study, researchers reported small molecules with inhibitory activity against SARS-CoV, SARS-CoV-2, and middle-east respiratory syndrome -CoV. First, they screened a set of carboxylic acid -containing molecules, henceforth denoted NBCoVs, and identified 20 compounds that were not pan-assay interference compounds .
Further, the team tested the effectiveness of best-performing NBCoVs against pseudoviruses of SARS-CoV-2 D614G and Gamma, Delta, and Omicron BA.1 and BA.4/5 variants of concern . NBCoV63 was the most potent against tested SARS-CoV-2 variants, with IC50 values of 34 – 96 nM and 26 – 105 nM in 293T-ACE2 and A549-AT cells, respectively.
By contrast, NBCoV35 and NBCoV36 were less potent against MERS-CoV, but NBCoV37 was highly potent. The team selected NBCoV63 based on the results and tested its activity against live SARS-CoV-2 Hong Kong isolate, Delta, and Omicron in the conventional plaque-reduction assay. The IC50 values of NBCoV63 were lower for the HK isolate and Delta variant but higher against Omicron than those of the control compound, remdesivir.
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