Determining the antiviral activity of two polyene macrolide antibiotics following treatment in Kidney Cells infected with SARS-CoV-2

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Abstract
Background There has been much speculation that polyene macrolide antibiotics, such as amphotericin B (AmB) and Nystatin (NYS) may have antiviral activity against several viruses including SARS-CoV-2. Objective The objective of this short communication was to determine the antiviral activity of two polyene macrolides, AmB and NYS, following treatment in kidney cells infected with SARS-CoV-2. Methods A serial dilution of AmB, NYS, and irbesartan (a drug known to bind to the ACE-2 receptor as a positive control) were then added (n=4 at each concentration) to the infected Vero’76 kidney cells in 100 µL media. Cells were also examined for contamination at 24 hours, and for cytopathic effect (CPE) and cytotoxicity (if noticeable) under a microscope at 48 hours. In a second study, AmB and Remdesivir were incubated in kidney cells infected with the virus and inhibition of the virus was determined by an immunoassay. Results and Conclusions Amphotericin B (AmB) showed a significant reduction in the TCID50 titer, with the 50% effective concentration (EC50) of 1.24 µM, which was 2.5 times lower than the cytotoxicity concentration. NYS and Irbesartan both exhibited substantially less active and would not be considered a suitable choice for further investigations. In addition, when measuring viral inhibition by immunoassay, AmB was significantly more potent than remdesivir (EC50 31.8 nM vs. 1.15 µM). Taken together, these preliminary findings suggest that AmB may have significant activity against SARS-CoV-2. However, further cell and animal studies are warranted.

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