Alpha and gamma mangostins inhibit wild-type B SARS-CoV-2 more effectively than the SARS-CoV-2 variants and the major target is unlikely the 3C-like protease.
| Autor: | Suroengrit A; Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.; Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand., Cao V; Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.; Interdisciplinary Program in Microbiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.; DaNang University of Medical Technology and Pharmacy, DaNang, 50200, Viet Nam., Wilasluck P; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.; Center of Excellence in Molecular Crop, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Deetanya P; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.; Center of Excellence in Molecular Crop, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Wangkanont K; Center of Excellence for Molecular Biology and Genomics of Shrimp, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.; Center of Excellence in Molecular Crop, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Hengphasatporn K; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan., Harada R; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan., Chamni S; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.; Center of Excellence in Natural Products and Nanoparticles (NP2), Chulalongkorn University, Bangkok, 10330, Thailand., Leelahavanichkul A; Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand., Shigeta Y; Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan., Rungrotmongkol T; Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.; Center of Excellence in Structural and Computational Biology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Hannongbua S; Center of Excellence in Structural and Computational Biology, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Chavasiri W; Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand., Wacharapluesadee S; Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand., Prompetchara E; Center of Excellence in Vaccine Research and Development, Chulalongkorn University (Chula-VRC), Bangkok, 10330, Thailand.; Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Boonyasuppayakorn S; Center of Excellence in Applied Medical Virology, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. |
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| Jazyk: | angličtina |
| Zdroj: | Heliyon [Heliyon] 2024 May 27; Vol. 10 (11), pp. e31987. Date of Electronic Publication: 2024 May 27 (Print Publication: 2024). |
| DOI: | 10.1016/j.heliyon.2024.e31987 |
| Abstrakt: | Background: Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and GM) were previously reported as potential 3C-like protease (3CL pro ) and Angiotensin-converting enzyme receptor 2 (ACE2)-binding inhibitors in silico . Objective: We aimed to evaluate two active compounds, AM and GM, from Garcinia mangostana for their antivirals against SARS-CoV-2 in live virus culture systems and their cytotoxicities using standard methods. Also, we aimed to prove whether 3CL pro and ACE2 neutralization were major targets and explored whether any additional targets existed. Methods: We tested the translation and replication efficiencies of SARS-CoV-2 in the presence of AM and GM. Initial and subgenomic translations were evaluated by immunofluorescence of SARS-CoV-2 3CL pro and N expressions at 16 h after infection. The viral genome was quantified and compared with the untreated group. We also evaluated the efficacies and cytotoxicities of AM and GM against four strains of SARS-CoV-2 (wild-type B, B.1.167.2, B.1.36.16, and B.1.1.529) in Vero E6 cells. The potential targets were evaluated using cell-based anti-attachment, time-of-drug addition, in vitro 3CL pro activities, and ACE2-binding using a surrogated viral neutralization test (sVNT). Moreover, additional targets were explored using combinatorial network-based interactions and Chemical Similarity Ensemble Approach (SEA). Results: AM and GM reduced SARS-CoV-2 3CL pro and N expressions, suggesting that initial and subgenomic translations were globally inhibited. AM and GM inhibited all strains of SARS-CoV-2 at EC Conclusion: AM and GM inhibited SARS-CoV-2 with the highest potency at the wild-type B and the lowest at the B.1.1.529. Multiple targets were expected to integratively inhibit viral replication in cell-based system. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.) |
| Databáze: | MEDLINE |
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