Molecular Docking Study of the Binding Interaction of Hydroxychloroquine, Dexamethasone and Other Anti-Inflammatory Drugs with SARS-CoV-2 Protease and SARS-CoV-2 Spikes Glycoprotein

Abstract

Aims: The outbreak of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still accountable for millions of deaths worldwide and declared as a global pandemic by the World Health Organisation. Despite efforts, there is still limited evidence available on a successful potent inhibitor with a low toxicity profile that can aid in the prevention and/or treatment of COVID-19. This study will focus on four main aspects: 1) screening 19 Food Drug and Administration (FDA) approved drugs using computational molecular docking; 2) assessing drug toxicity profiles using biological data; 3) recommending potential therapies against COVID-19 and 4) supplementing currently used therapies. Methods: 19 FDA approved drugs were investigated against the crystal structure of SARS-CoV-2 protease (6LU7) and SARS-CoV-2 glycoprotein (6VXX) using a computational molecular docking software, Molecular Operating Environment (MOE). Separately, on MOE, 6LU7 and 6VXX were loaded, prepared, and the binding pockets located. The drug’s canonical SMILES were imported, minimised, and docked on the prepared proteins using a search algorithm to establish the highest stability conformation. Drugs were ranked depending on binding properties and biological data to assess safety; steric clashes and voids in the binding site were also analysed. Results and discussion: Out of the nineteen (19) FDA approved drugs, 18 inhibited 6LU7 and 13 inhibited 6VXX. High-ranked drugs based on binding properties for 6LU7 were hydroxychloroquine, dexamethasone, naproxen, etoricoxib, and ibuprofen. For 6VXX were hydroxychloroquine, celecoxib, etoricoxib, meloxicam, and parecoxib. Considering safety profile, the top 3 drugs in descending order for 6LU7 were etoricoxib, naproxen and dexamethasone and for 6VXX were etoricoxib, meloxicam, and parecoxib. Compared to the literature, the results were consistent for dexamethasone which was effective against 6LU7. However, for hydroxychloroquine and ibuprofen, there was conflicting literature regarding safety and efficacy. Conclusion and future work: The findings suggest that against COVID-19 etoricoxib might be effective as a therapeutic and prophylactic measure. Naproxen and dexamethasone would be more effective as treatment only while meloxicam and parecoxib as prophylaxis. However, future studies are needed to validate these findings. Compared to previous literature, the findings in this study also support the use of dexamethasone over hydroxychloroquine and ibuprofen for COVID-19 based on the binding and safety properties. Despite this, future research should explore the impressive binding properties displayed by hydroxychloroquine and ibuprofen to aid in developing a new drug against COVID-19.