Discovery of Cysteine and Its Derivatives as Novel Antiviral and Antifungal Agents

Abstract

Based on the structure of the natural product cysteine, a series of thiazolidine-4-carboxylic acids were designed and synthesized. All target compounds bearing thiazolidine-4-carboxylic acid were characterized by ¹H-NMR, ¹³C-NMR, and HRMS techniques. The antiviral and antifungal activities of cysteine and its derivatives were evaluated in vitro and in vivo. The results of anti-TMV activity revealed that all compounds exhibited moderate to excellent activities against tobacco mosaic virus (TMV) at the concentration of 500 μg/mL. The compounds cysteine (<b>1</b>), <b>3</b>-<b>4</b>, <b>7</b>, <b>10</b>, <b>13</b>, <b>20</b>, <b>23</b>, and <b>24</b> displayed higher anti-TMV activities than the commercial plant virucide ribavirin (inhibitory rate: 40, 40, and 38% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively), especially compound <b>3</b> (inhibitory rate: 51%, 47%, and 49% at 500 μg/mL for inactivation, curative, and protection activity in vivo, respectively) with excellent antiviral activity emerged as a new antiviral candidate. Antiviral mechanism research by TEM exhibited that compound <b>3</b> could inhibit virus assembly by aggregated the 20S protein disk. Molecular docking results revealed that compound <b>3</b> with higher antiviral activities than that of compound <b>24</b> did show stronger interaction with TMV CP. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these cysteine derivatives displayed broad-spectrum fungicidal activities. Compound <b>16</b> exhibited higher antifungal activities against <i>Cercospora arachidicola Hori</i> and <i>Alternaria solani</i> than commercial fungicides carbendazim and chlorothalonil, which emerged as a new candidate for fungicidal research.