Computational Studies of Selected Transition Metal Complexes as Potential Drug Candidates against the SARS‐CoV‐2 Virus

Pal, Maynak; Musib, Dulal; Zade, Aniket J.; Chowdhury, Neeta; Roy, Mithun

The earth has witnessed the greatest global health crisis due to the outbreak of the SARS‐CoV‐2 virus in late 2019, resulting in the pandemic COVID‐19 with 3.38 million mortality and 163 million infections across 222 nations. Therefore, there is an urgent need for an effective therapeutic option against the SARS‐CoV‐2 virus. Transition metal complexes with unique chemical, kinetic and thermodynamic properties have recently emerged as the viable alternative for medicinal applications. Herein, the potential application of selected antiviral transition metal‐based compounds against the SARS‐CoV‐2 virus was explored in silico. Initially, the transition metal‐based antiviral compounds (1‐5) were identified based on the structural similarity of the viral proteins (proteases, reverse transcriptase, envelop glycoproteins, etc.) of HIV, HCV, or Influenza virus with the proteins (S‐protein, RNA‐dependent RNA polymerase, proteases, etc) of SARS‐CoV‐2 virus. Hence the complexes (1‐5) were subjected to ADME analysis for toxicology and pharmacokinetics report and further for the molecular docking calculations, selectively with the viral proteins of the SARS‐CoV‐2 virus. The molecular docking studies revealed that the iron‐porphyrin complex (1) and antimalarial drug, ferroquine (2) could be the potential inhibitors of Main protease (M(pro)) and spike proteins respectively of SARS‐CoV‐2 virus. The complex 1 exhibited high binding energy of −11.74 kcal/mol with the M(pro) of SARS‐CoV‐2. Similarly ferroquine exhibitred binding energy of −7.43 kcal/mol against spike protein of SARS‐CoV‐2. The complex 5 also exhibited good binding constants values of −7.67, −8.68 and −7.82 kcal/mol with the spike protein, M(pro) and RNA dependent RNA polymerase (RdRp) proteins respectively. Overall, transition metal complexes could provide an alternative and viable therapeutic solution for COVID‐19.