The most common host entry point of human adapted coronaviruses (Covs) including the recent pandemic SARS-CoV-2 is through the initial colonization in the nostril and mouth region, which is responsible for the spread of the infection. Most recent studies suggest that the commercially available oral and nasal rinse products are effective in inhibiting the viral replication. However, the anti-viral mechanism of the active ingredients present in the oral rinses have not been individually studied. Several studies have suggested that the viral proteases play a major role during the viral replication and therefore serve as a better drug targets. PLpro and 3CLpro are proteases that are essential for the replication of the emerging infectious CoVs including SARS-CoV-2. Therefore, in the present study we have investigated the enzymatic inhibitory activity of active ingredients of commonly used oral rinse products against SARS-CoV-2 PLpro and 3CLpro enzymes. We have performed the <i>in vitro</i> enzymatic assay in the presence of aloin B, chlorhexidine, eucalyptol, hexetidine, menthol, triclosan, methyl salicylate, sodium fluoride and povidone iodide to investigate their inhibitory activity against two important proteases of SARS-CoV-2. Importantly, we observed that only aloin B effectively inhibits the PLpro but not the 3CLpro. Structural analysis of aloin B interaction with PLpro revealed that, aloin B forms Hydrogen bond with Tyr268 of PLpro, which is critical for its enzymatic activity. Taken together, these studies suggest that aloin B, a small molecular weight compound present in aloe plant inhibits the enzymatic activity of PLpro of SARS-CoV-2 suggesting the potential beneficial effect in reducing the replication of SARS-CoV-2 virus. However, these studies need to be validated with pre-clinical and clinical studies.

Selective inhibition of SARS COV-2, papain-like protease (PLpro) enzyme in vitro by aloin B an active ingredient of aloe vera

ACS Fall 2021

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