ABSTRACT
The development of efficacious therapeutic agents with relatively low or no level of toxicity was necessitated due to the reemergence of coronavirus. The present study investigated the inhibitory potentials of 4-aminoquinolines (amopyroquine, mefloquine, amodiaquine, bispyroquine, quinine, chloroquine, hydroxychloroquine, chloroquine hydrochloride, chloroquine sulfate, cycloquine, and quinacrine) against selected structural and nonstructural proteins of SARS-CoV-2. The 4-aminoquinolines with higher binding affinities were selected for physicochemical properties, absorption, distribution, metabolism, and excretion (ADME) analysis. The binding energies were computed with Autodock vina screening software while physicochemical properties and ADME parameters were predicted through SwissADME server. Amopyroquine, mefloquine, bispyroquine, and quinine had the highest binding affinities with the amino acids in the pocket of the SARS-CoV-2 structural proteins (envelope, membrane, nucleocapsid, and spike) and nonstructural proteins (3-chymotrypsin-like protease, papain-like protease, and RNA-dependent RNA polymerase) compared with chloroquine and other 4-aminoquinolines used in this study. In addition, the pharmacokinetics and physicochemical parameters revealed that amopyroquine, mefloquine, bispyroquine, and quinine demonstrated good drug-like properties with relatively low toxic effects. The data from this study provide evidence that some of the 4-aminoquinolines can be repurposed and further developed as therapeutic agents with potentials to inhibit coronavirus cellular entry and replication. © 2022 Elsevier Inc. All rights reserved.