Screening of preferential binding affinity of selected natural compounds to SARS-CoV-2 proteins using in silico methods

Objectives: The global burden of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the corona virus disease-19 (COVID-19) is enormous No definitive treatment and prophylactic guidelines for COVID-19 currently exist except for physical distancing and aerial barriers between individuals This work explored the natural compound-binding efficiency of SARS-CoV-2 proteins essential for host cell interaction and infection Methods: The binding activity of artemisinin to SARS-CoV-2 spike glycoprotein (Protein Data Bank (PDB) ID: 6VYB), SARS-CoV-2 main protease (3C-like main protease (3CLpro);PDB ID: 6Y84) and SARS-CoV-2 papain-like protease (PLpro;PDB ID: 6W9C), were tested using in silico methods Moreover, chloroquine and hesperidin were used as the positive control of binding affinity and proven therapeutic effect, respectively Results: The highest affinities for binding to all tested SARS-CoV-2 proteins are observed for hesperidin (-5 8,-10 0, and -8 1 kcal/mol), then for artemisinin (-4 8,-8 3, and -6 0 kcal/mol), and the lowest for chloroquine (-4 1,-8 2, and -4 8 kcal/mol) Artemisinin, hesperidin, and chloroquine had similar positioning toward targeted proteins at specific sites when these interactions were visualized Conclusion: This study shows that artemisinin has the potential to bind and inhibit the SARS-CoV-2 spike protein, the 3CLpro main protease, and PLpro proteinase similar to hesperidin and chloroquine that have been proven as antivirals in previous preclinical and clinical studies