Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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).
【저자키워드】 COVID-19, Drug repurposing, Chloroquine, spike, protease, MD simulation, 【초록키워드】 coronavirus disease, SARS-CoV-2, coronavirus, pandemic, drug, docking, virus, antimalarial, binding affinity, Spike protein, Molecular dynamics simulation, Receptor binding domain, stability, RBD, target, binding, food, Analysis, antimalarial drug, acute respiratory syndrome, in silico Approach, domain, virion, high stability, objective, effective, bind, Result, caused, investigated, was performed, exhibited, complexes, Paromomycin, 【제목키워드】 inhibit,