Triple-target small molecule for PRRSV and ASFV infections.

Pigs are vital sources of food and biological products. However, viruses such as porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV) pose significant threats to the global swine industry, resulting in substantial financial losses. Currently, there are no available drugs or effective vaccines to combat these viruses. This study presents a small molecule, denoted as C14, which demonstrates promising potential to target porcine CD163, RNA-dependent RNA polymerase (RdRp) of PRRSV, and S273R of ASFV, and exhibits activity against both PRRSV (half maximal effective concentration [EC50] = 0.34 μM) and ASFV (EC50 < 0.1 μM). By employing the strategy of similar topological structure binding properties of protein targets (STSBPT), interactions between C14 and targets were further analysed. The results indicate that the 5-Å regions of C14 within the active pockets of these macromolecular targets exhibit highly similar structural features, which may facilitate the development of antiviral drugs. Chemical synthesis, docking simulations, and antiviral activity assays were further conducted, and it was found that the structure of C14 is devoid of redundant elements, making it a prime candidate as core scaffold for subsequent structural optimization. This study provides a valuable reference for the development of multi-target antiviral drugs against PRRSV and ASFV.