Evaluation of RevX solution extract as a potential inhibitor of the main protease of SARS-CoV-2—In vitro study and molecular docking

The main protease (M^pro) of SARS-CoV-2 is a protease necessary for viral polyprotein processing and maturation. M^pro cleaves the polypeptide sequence after the glutamine residues. There is no known cellular protease with this substrate specificity in humans; therefore, it is considered an attractive drug target. Previously, fermented sorghum extract RevX (trademark of Revolutrx INC.) solution significantly alleviated physical decline and complications in a patient with lung adenocarcinoma, suggesting the role of bioactive components in RevX solution. To further explore whether the bioactive components in RevX solution exhibit other biological activities, such as antiviral effects, we investigated its inhibitory effect on the M^pro of SARS-CoV-2 virus. We report herein that the solid extract of the RevX solution exhibits an efficacious M^pro inhibitory activity, with IC₅₀ of 2.07 ± 0.38 μg/mL. Molecular docking of sterol-like components in the RevX extracts identified by MS shows that the three sterol-like molecules can bind to the active region of the GC376-M^pro complex, supporting the structure-function relationship. Combined with its ability to significantly alleviate the body's immunity decline and to inhibit the activity of SARS-CoV-2 M^pro, RevX solution may provide a possible alternative supportive treatment for patients with COVID-19.