In silico analysis of Balsaminol as anti-viral agents targeting SARS-CoV-2 main protease, spike receptor binding domain and papain-like protease receptors

Abstract

Abstract Plant-derived phytochemicals from medicinal plants are becoming increasingly attractive natural sources of antimicrobial and antiviral agents due to their therapeutic value, mechanism of action, level of toxicity and bioavailability. The continued emergence of more immune-evasive strains and the rate of resistance to current antiviral drugs have created a need to identify new antiviral agents against SARS-CoV-2. This study investigated the antiviral potential of balsaminol from Momordica balsamina against SARS-CoV-2. In this study, three Food and Drug Administration (FDA) COVID-19 approved drugs namely; nirmatrelvir, ritonavir and remdesivir were used as positive control. In silico approaches including molecular docking based virtual screening, protein quality assessment models, pharmacokinetics, drug-like properties, toxicity profiling and Discovery Studio Visualizer were used to predict therapeutic targets on SARS-CoV-2 receptor proteins. All balsaminols used in this study exhibited negative binding energies with 6LU7, 6VW1 and 7CMD, indicating their strong binding affinity to the target proteins. Balsaminol C had the highest binding affinity of -9.3 kcal/mol with the main SARS CoV-2 protease (6LU7), in agreement with molecular interaction studies. Balsaminol E had a binding affinity of -7.8 kcal/mol with the spike receptor binding domain (6VW1) and balsaminol F had a binding energy of -7.8 with the papain-like protease (7CMD) when compared to ritonavir, nirmatrelvir and rem-desivir. However, the ADMET and drug-like profile of Balsaminol F shows it to be a better potential drug candidate and a good inhibitor against the docked SARS-CoV-2 target proteins, thus recommending further preclinical studies.