Natural inhibitors for severe acute respiratory syndrome coronavirus 2 main protease from Moringa oleifera, Aloe vera, and Nyctanthes arbor-tristis: molecular docking and ab initio fragment molecular orbital calculations.

The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly worldwide, and new drug treatments for COVID-19 are urgently required. To find the potential inhibitors against the main protease (Mpro) of SARS-CoV-2, we investigated the inhibitory potential of naturally occurring compounds from the plants Moringa oleifera, Aloe vera, and Nyctanthes arbor-tristis, using molecular docking, classical molecular mechanics optimizations, and ab initio fragment molecular orbital (FMO) calculations. Of the 35 compounds that we simulated, feralolide from Aloe vera exhibited the highest binding affinity against Mpro. Therefore, we proposed novel compounds based on the feralolide and investigated their binding properties to Mpro. The FMO results indicated that the introduction of a hydroxyl group into feralolide significantly enhances its binding affinity to Mpro. These results provide useful information for developing potent Mpro inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s11224-022-02021-y.

Proposal of novel natural inhibitors of severe acute respiratory syndrome coronavirus 2 main protease: Molecular docking and ab initio fragment molecular orbital calculations.

This paper proposes natural drug candidate compounds for the treatment of coronavirus disease 2019 (COVID-19). We investigated the binding properties between the compounds in the Moringa oleifera plant and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 using molecular docking and ab initio fragment molecular orbital calculations. Among the 12 compounds, niaziminin was found to bind the strongest to Mpro. We furthermore proposed novel compounds based on niaziminin and investigated their binding properties to Mpro. The results reveal that the introduction of a hydroxyl group into niaziminin enhances its binding affinity to Mpro. These niaziminin derivatives can be promising candidate drugs for the treatment of COVID-19.