Effects of organic salts of virucidal and antiviral compounds from Nelumbo nucifera and Kaempferia parviflora against SARS-CoV-2

The present work investigates virucidal and antiviral compounds in the extracts of seed embryos of a lotus, Nelumbo nucifera, and a Thai ginseng, Kaempferia parviflora. Separation of the extracts led to the identification of antiviral compounds against SARS-CoV-2. Neferine (1) and nuciferine (3) from N. nucifera, as well as their respective HCl salts (2 and 4), exhibited virucidal and antiviral activities against SARS-CoV-2. Virucidal activity of neferine salt (2) (EC₅₀ 4.78 µM) was 7.5 times better than its free-base, neferine (1) (EC₅₀ 36.01 µM), and the salt (2) also improved the selectivity index (SI), showing less cytotoxicity than 1. This work demonstrates that organic salts have an impact on biological activities. A crude extract of K. parviflora rhizomes displayed virucidal activity (EC₅₀ 42.11 µg/mL) and antiviral activity (EC₅₀ 39.28 µg/mL). Isolation of a crude extract of K. parviflora rhizomes led to the identification of nine flavonoids (5-13). Among these flavonoids, only 5,7,4'-trimethoxyflavone (8) was found to show virucidal (EC₅₀ 437.90 µM) and antiviral (EC₅₀ 50.97 µM) activities against SARS-CoV-2. However, flavonoids (5-13) did not inhibit SARS-CoV-2 3CL^pro enzyme at the concentrations of 10 µM and 100 µM. In conclusion, our data underscores the therapeutic potential of N. nucifera and K. parviflora derived bioactive compounds against SARS-CoV-2.