Ning jing zhi yuan12/14/2023 The S2 subunit is further cleaved by host proteases, including the transmembrane serine protease 2 (TMPRSS2) and furin, which results in the dissociation of the S1 and the S2-mediated membrane fusion process ( Cheng et al., 2020 Shang et al., 2020 Li et al., 2021). The SARS-CoV-2 infection begins when virus particles attach to host cells due to interactions between S1 and ACE2 ( Lan et al., 2020 Walls et al., 2020 Wang et al., 2020 Wrapp et al., 2020). The S2 subunit has a fusion domain at the C-terminal of the S protein that fuses viral and cellular membranes ( Li, 2016 Yan et al., 2020). The S1 subunit has a receptor binding domain (RBD) at the N-terminal of the S protein, which binds to a critical host receptor: the angiotensin-converting enzyme-2 (ACE2). The S protein is composed of two functional subunits: S1 and S2. The RNA genome of the SARS-CoV-2 is approximately 30 K nucleotides long and encodes four structure proteins, including a spike glycoprotein (S), an envelope protein (E), a membrane protein (M), and a nucleoprotein (N) ( Chen et al., 2020). SARS-CoV-2, which is the largest positive-strand RNA virus, is a member of the Coronaviridae family which includes the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) ( Collaborators, 2020 Zhou et al., 2020). More than 3.3 million cases resulted in death tolls ( WHO, 2021). Until mid-May 2021, more than 162 million COVID-19 cases were recorded worldwide. Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused coronavirus disease 2019 (COVID-19), which is a severe pandemic with a wide spectrum of clinical symptoms, ranging from asymptomatic infection or a mild, flu-like illness to life-threatening diseases including severe pneumonia and severe acute respiratory syndrome (SARS) ( Collaborators, 2020 Guan et al., 2020 Zhu et al., 2020). Moreover, JGF may be applicable as an adjuvant preventive strategy against SARS-CoV-2 infection in addition to the use of vaccines. Together, these findings suggest that JGF may improve the COVID-19 like symptoms and inhibit viral infection. Mice that inhale JGF exhibit reduced ACE2 and TMPRSS2 protein levels in lung tissues. Mechanistically, JGF induces lysosomal-dependent ACE2 degradation and suppresses mRNA and the protein levels of TMPRSS2 in human lung WI-38 and MRC-5 cells. Functional studies show that JGF inhibits the formation of syncytium and reduces the formation of viral plaque. This study produces a traditional Chinese medicine formula, Jing Guan Fang (JGF), based on ancient medical texts, and examines the efficacy and the mechanism by which JGF prevents viral infections. Developing adjuvant therapies which could prevent the virus from binding to cells may impair viral infection. Program, National Yang Ming Chiao Tung University, Taipei, TaiwanĬOVID-19 is a global epidemic. 5Branch of Linsen Chinese and Kunming, Taipei City Hospital, Taipei, Taiwan.4National Research Institute of Chinese Medicine, Taipei, Taiwan.3Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.2Institute of Biophotonics, National Yang Ming Chiao Tung University, Taipei, Taiwan.1Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.Yueh-Hsin Ping 1,2 Hsin Yeh 3 Li-Wei Chu 1 Zhi-Hu Lin 3 Yin-Chieh Hsu 3 Lie-Chwen Lin 4 Chung-Hua Hsu 1,3,5 Shu-Ling Fu 3 * Tung-Yi Lin 3,6 *
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