Kaempferol as a novel inhibitor of SARS-CoV-2 RNA-dependent RNA polymerase
Alessandro Medoro, Francesca Benedetti, Mariano Intrieri, Tassadaq Hussain Jafar, Sawan Alì, Truong Tan Trung, Daniela Passarella, Saba Ismail, Davide Zella, Giovanni Scapagnini, Sergio Davinelli · Journal of Biomolecular Structure and Dynamics · 2024
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has quickly become a global health pandemic. Among the viral proteins, RNA‐dependent RNA polymerase (RdRp) is responsible for viral genome replication and has emerged as a promising target against SARS‐CoV‐2 infection. Dietary bioactive compounds represent an important source of evolutionarily optimized molecules with antiviral properties against SARS-CoV-2 RdRp. We investigated the inhibitory potential effects of different phytochemicals against SARS-CoV-2 RdRp, including andrographolide, kaempferol, resveratrol, and silibinin. Unlike the other investigated compounds, kaempferol exhibited a significant dose-dependent in vitro inhibition of SARS-CoV-2 RdRp activity. To assess the binding interactions and stability of the SARS-CoV-2 RdRp-kaempferol complex, we performed in silico techniques, including molecular docking, quantum chemical calculation, and molecular dynamics simulations. We found strong binding affinities and stability between kaempferol and SARS-CoV-2 RdRp variants (Wuhan and Omicron). These findings provide valuable insights into the antiviral properties of kaempferol as a stable inhibitor of SARS-CoV-2 RdRp.