A commentary published in “SLAS Discovery” recommended that nimesulide should be considered for inclusion in the list of drugs to be tested for identifying the co-adjuvants in managing COVID-19. It highlighted the presence of a molecular basis, besides the recently published in silico studies, for considering nimesulide as an additional agent in the ongoing trials for combating COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is one of the human membrane proteins that is known to be docked by the virus. It is proposed to be responsible for SARS-CoV-2 entrance in the host cells. Recently, the three-dimensional structure of ACE2 has been procured, demonstrating its physical interaction with sodium-dependent neutral amino acid transporter (B0AT1 [SLC6A19]). B0AT1 is a plasma membrane transporter that is implicated in the trafficking of amino acids in cells.

The receptor targeted by coronavirus is a supercomplex formed by ACE2-B0AT1 dimer. ACE2 forms a heterodimer with B0AT1 (ACE2-B0AT1), in which ACE2 effectively binds the protein of the virus and B0AT1 stabilizes the heterodimer.

Nimesulide was found to impair the transport function of B0AT1 (a serendipity occurrence). The biochemical data together with computational analysis illustrated that nimesulide completely abolished B0AT1 transport function by attaining a high-affinity pocket accessible from the extracellular milieu as depicted in the following figure:

Thus, nimesulide, a strong inhibitor of the B0AT1 subunit of the SARS-CoV-2 receptor, may be considered as a therapeutic adjuvant to manage COVID-19.