Ting‑Hsu Chena†, Zi‑Han Shenb†, May‑Jywan Tsaic, Ching‑Feng Wengd*, Max K. Leonge*
aGraduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan, bDepartment of Clinical Medicine, Xiamen Medical College, Xiamen, Fujian, China, cDepartment of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, dFunctional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Fujian, China, eDepartment of Chemistry, National Dong Hwa University, Hualien, Taiwan
†Both authors contributed equally to this work.
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Objectives: The recent global coronavirus disease 2019 (COVID‑19) pandemic, resulting from infection by severe acute respiratory syndrome coronavirus‑2 (SARS‑CoV‑2), can cause severe and fatal pneumonia along with other life‑threatening complications. Materials and Methods: The rare and limited accessibility of approved therapeutic agents or vaccines is of great distress. Swiftly working on designing and identifying inhibitors against all possible viral key protein targets, seven key SARS‑CoV‑2 viral enzymes were selected as targets, particularly in the action on the virus‑entry, viral replication, and immune evasion of COVID‑19. Papain‑like protease, main protease, RNA‑dependent RNA polymerase, endoribonuclease (nsp15), receptor‑binding domain‑angiotensin‑converting enzyme 2, transmembrane serine protease 2 (TMPRSS2), and 2’‑O‑ribose methyltransferase (2′MTase), which were subjected to an unbiased in silico screening against 22 small molecules originating from Garcinia linii concomitantly with Remdesivir, Nirmatrelvir, and Molnupiravir were approved by Food and Drug Administration as repurposing drugs against SARS‑CoV‑2 invasion. Results: The in silico results showed that natural bioactive compounds containing α‑Tocopheryolquinone, 6β‑Hydroxystigmast‑4‑en‑3‑one, Squalene, Rutin and Quercetin have a high binding affinity with seven selected viral protein targets concurrently with the preference of absorption, distribution, metabolism, excretion, and toxicity and drug‑likeness. Conclusion: This study provides potential phytoactive compounds from G. linii through multi‑target screen with molecular dynamic simulation for combating COVID‑19 pandemics that need further experimental validation to confirm the prospective efficacy.
Keywords: Garcinia linii, Immune evasion, Severe acute respiratory syndrome coronavirus‑2, Viral proliferation, Virus entry
