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. 2022 Mar;8(3):e09034.
doi: 10.1016/j.heliyon.2022.e09034. Epub 2022 Feb 28.

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

Feng-Pai Chou  1   2 , Chia-Chun Liu  3 , Huynh Nguyet Huong Giang  4 , Sheng-Cih Huang  1 , Hsiu-Fu Hsu  3 , Tung-Kung Wu  1   2
Affiliations

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

Feng-Pai Chou et al. Heliyon. 2022 Mar.

Abstract

The main protease (Mpro) of SARS-CoV-2 is a protease necessary for viral polyprotein processing and maturation. Mpro 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 Mpro of SARS-CoV-2 virus. We report herein that the solid extract of the RevX solution exhibits an efficacious Mpro 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-Mpro 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 Mpro, RevX solution may provide a possible alternative supportive treatment for patients with COVID-19.

Keywords: Antiviral drug; GC-376; Mpro; Sorghum; Sterol.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SARS-CoV-2 genome organization. (A) SARS-CoV-2 genomic RNA, encoding non-structural proteins (NSPs), ORF 1ab which can be directly translated into two polyproteins pp1a and pp1b, and structural and accessory proteins. (B) Schematic representation of non-structural polyprotein cleavage sites. Two viral proteases, a papain-like protease (PLpro, green arrow) and a main protease (Mpro, red arrow), cleave the two polyproteins to generate 16 NSPs (Ullrich and Nitsche, 2020). The Mpro recognizes and cleaves the virus non-structural polyprotein at 11 sites. The PLpro cleaves the virus non-structural polyprotein at 3 sites.
Figure 2
Figure 2
The inhibitory activity of SARS-CoV-2 Mpro in serial dilutions of (A) solid, (B) organic, and (C) water fractions.
Figure 3
Figure 3
Molecular docking of GC376 and SARS-CoV-2 Mpro. (A) Ligplot image showing both hydrogen and hydrophobic interactions by GC376 and Mpro, and (B) Docking pose of GC376 against Mpro.
Figure 4
Figure 4
Molecular docking of J3 and SARS-CoV-2 Mpro. (A) Ligplot image showing both hydrogen and hydrophobic interactions by J3 and Mpro, and (B) Docking pose of J3 against Mpro.
Figure 5
Figure 5
Molecular docking of J4 and SARS-CoV-2 Mpro. (A) Ligplot image showing both hydrogen and hydrophobic interactions by J4 and Mpro, and (B) Docking pose of J4 against Mpro.
Figure 6
Figure 6
Molecular docking of J11 and SARS-CoV-2 Mpro. (A) Ligplot image showing both hydrogen and hydrophobic interactions by J11 and Mpro, and (B) Docking pose of J11 against Mpro.
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