Paromomycin: A potential dual targeted drug effectively inhibits both spike (S1) and main protease of COVID-19

•With the increasing number of people suffering from COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic.•In this study, we propose a single drug – paromomycin – against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Based upon docking scores and molecular dynamics simulation, paromomycin was found to have strong binding affinity for both of the targets of coronavirus.•15 anti-malarial drugs including chloroquine were also investigated against both targets using in-silico approach resulting in no effective binding.•Paromomycin, a broad-spectrum aminoglycoside antimicrobial drug that was originally used to treat acute and chronic intestinal infections, may also be of potential use in the treatment of COVID-19, as one of the major symptoms in COVID-19 includes gastrointestinal disturbance.•Clinical trials are needed to confirm the efficacy of paromomycin against SARS-CoV-2. With the increasing number of people suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for the current situation. In a quest to find a potential drug against this virus, 15 antimalarial drugs (including chloroquine) and 2413 US Food and Drug Administration-approved drugs were investigated for activity against both the protease and spike proteins of SARS-CoV-2 using an in silico approach. Molecular docking analysis followed by molecular dynamics simulation was performed to estimate the binding and stability of the complexes. This study identified a single drug – paromomycin – with activity against two targets of SARS-CoV-2, i.e., spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity for both targets of coronavirus. The results also showed that no antimalarial drug exhibited effective binding for either S1 or protease. This study found that paromomycin may be an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion, but also to the spike domain, with high stability. Furthermore, none of the antimalarial drugs showed strong binding affinity for either protease or the receptor binding domain (RBD).