Article
Pharmacology & Pharmacy
Somasundaram Raghavan, M. Dennis Leo
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is a significant global health crisis. The range of symptoms among COVID-19 patients varies from life-threatening to mild or asymptomatic, posing challenges for identification, quarantine, and treatment. The emergence of Long COVID, characterized by unusual symptoms among survivors, is concerning due to limited understanding and treatment options. Recent evidence suggests that histamine and vascular inflammation might contribute to some Long COVID symptoms. Famotidine, a commonly used H2 receptor blocker, has been shown to prevent adverse outcomes in COVID-19 patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Shiho Tanaka, Gard Nelson, C. Anders Olson, Oleksandr Buzko, Wendy Higashide, Annie Shin, Marcos Gonzalez, Justin Taft, Roosheel Patel, Sofija Buta, Ashley Richardson, Dusan Bogunovic, Patricia Spilman, Kayvan Niazi, Shahrooz Rabizadeh, Patrick Soon-Shiong
Summary: The study identified an ACE2 decoy that can effectively combat SARS-CoV-2 variants, offering a treatment option. The use of MD simulation to predict ACE2 sequence substitutions and screen candidate ACE2 decoys enhances efficacy against variants.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Yusen Xiang, Mengge Wang, Hongzhuan Chen, Lili Chen
Summary: The global spread of the COVID-19 pandemic caused by SARS-CoV-2 has highlighted the urgent need for rapid drug development in the absence of precise treatment. The virus S protein plays a crucial role in vaccine and drug development, with a focus on inhibitors targeting SARS-CoV-2 S protein, ACE2, and viral infection-associated enzymes. The review provides valuable information for potential antiviral agent discovery and development in combating SARS-CoV-2, with future exploration of more targeted prevention and treatment drugs expected with advanced technology.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Farzaneh Jafary, Sepideh Jafari, Mohamad Reza Ganjalikhany
Summary: The novel coronavirus SARS-CoV-2, responsible for COVID-19, binds to ACE2 on lung cells with higher affinity compared to SARS-CoV. Critical mutations in the spike glycoprotein of SARS-CoV-2 lead to increased binding affinity with ACE2, providing insights for potential drug design to inhibit the virus-cell interaction.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Ling Ma, Yali Li, Ting Shi, Zhiling Zhu, Jianyuan Zhao, Yongli Xie, Jiajia Wen, Saisai Guo, Jing Wang, Jiwei Ding, Chen Liang, Guangzhi Shan, Quanjie Li, Mei Ge, Shan Cen
Summary: A series of teicoplanin derivatives, glycopeptide antibiotics, have been found to bind to the S protein of SARS-CoV-2, interrupt its interaction with ACE2 receptor, and selectively inhibit viral entry. These derivatives also inhibit the entry of the Delta and Omicron variants. Therefore, they hold great promise as pan-SARS-CoV-2 inhibitors.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Francesco Nappi, Sanjeet Singh Avtaar Singh
Summary: The inflammatory process triggered by SARS-CoV-2 infection plays a crucial role in its pathogenesis, leading to severe systemic symptoms through various pathways. The role of endothelial dysfunction and thrombosis in this process has not been fully explored. This review aims to understand the pathogenic mechanisms of these inflammatory triggers and their association with thrombotic complications, while also examining a case of carotid artery thrombosis following SARS-CoV-2 infection.
Article
Multidisciplinary Sciences
Tomokazu Yamaguchi, Midori Hoshizaki, Takafumi Minato, Satoru Nirasawa, Masamitsu N. Asaka, Mayumi Niiyama, Masaki Imai, Akihiko Uda, Jasper Fuk-Woo Chan, Saori Takahashi, Jianbo An, Akari Saku, Ryota Nukiwa, Daichi Utsumi, Maki Kiso, Atsuhiro Yasuhara, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Yuji Fujino, Satoru Motoyama, Satoshi Nagata, Josef M. Penninger, Haruhiko Kamada, Kwok-Yung Yuen, Wataru Kamitani, Ken Maeda, Yoshihiro Kawaoka, Yasuhiro Yasutomi, Yumiko Imai, Keiji Kuba
Summary: Endogenous ACE2 is a receptor for SARS-CoV-2 and a recombinant soluble ACE2 protein can act as a decoy to inhibit virus infection. The ACE2-like enzyme B38-CAP is shown to be protective against SARS-CoV-2-induced lung injury, providing potential therapeutic strategies for COVID-19 patients.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Hristo L. Svilenov, Florent Delhommel, Till Siebenmorgen, Florian Ruehrnoessl, Grzegorz M. Popowicz, Alwin Reiter, Michael Sattler, Carsten Brockmeyer, Johannes Buchner
Summary: The solution structure, stability, and dynamics of a broadly-acting antiviral ACE2-IgG-Fc fusion protein are determined. Small chemical compounds binding to ACE2 can be used to drastically increase the thermal stability of the ACE2 domain. Our findings reveal a general concept for stabilizing the labile receptor segments of therapeutic antiviral fusion proteins by chemical compounds.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Alicia M. Matthews, Thomas Biel, Uriel Ortega-Rodriguez, Vincent Falkowski, Xin Bush, Talia Faison, Hang Xie, Cyrus Agarabi, V. Ashutosh Rao, Tongzhong Ju
Summary: This study established CHO cell lines that express ACE2-Fc proteins and partially characterized their physicochemical properties and spike protein binding. The results show that the fusion proteins are heavily N-glycosylated, sensitive to thermal stress, and bind to different spike protein variants with varying affinity. This research provides a proof-of-concept production strategy for ACE2-Fc fusion glycoproteins that could be used in the development of alternative countermeasures against emerging SARS-CoV-2 variants.
Article
Pharmacology & Pharmacy
Steven D. Brooks, Rachel L. Smith, Aline S. Moreira, Hans C. Ackerman
Summary: Lisinopril increases ACE2 expression in tissues relevant to COVID-19, while adding losartan prevents the lisinopril-induced increase. A sex difference was observed with higher ACE2 levels in the kidneys of male mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Agnieszka Dettlaff-Pokora, Julian Swierczynski
Summary: SARS-CoV-2 impairs the renin-angiotensin-aldosterone system by binding the ACE2 enzyme, leading to an increase in angiotensin 2 and a decrease in angiotensin (1-7), potentially worsening damage to the lungs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Tatsuya Maruhashi, Yukihito Higashi
Summary: COVID-19 caused by SARS-CoV-2 poses a worldwide challenge to healthcare systems, with thromboembolism being a major complication contributing to high morbidity and mortality in severe cases. Studies suggest that the direct infection of endothelial cells by SARS-CoV-2 may lead to endothelial dysfunction, resulting in thrombotic complications and severe outcomes in COVID-19 patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Microbiology
Sarah Alabsi, Atharva Dhole, Sameh Hozayen, Scott A. Chapman
Summary: Angiotensin-converting enzyme 2 (ACE2) plays a crucial role as a counterregulatory enzyme in the renin-angiotensin system (RAS), exerting protective actions against vasoconstriction, inflammation, and fibrosis. ACE2 serves as the binding site for the viral spike protein of SARS-CoV-2, facilitating its entry into ACE2-expressing tissue cells. Various factors, including viral variants, patient characteristics, and ACE2 expression levels, contribute to the severity and complications of COVID-19 infection. The impact of medications that alter ACE2 receptor expression on disease progression and outcomes remains uncertain. This review aims to discuss the interrelation between SARS-CoV-2, ACE2, and factors influencing the variability of ACE2 expression and the severity of COVID-19 infection.
Article
Biochemistry & Molecular Biology
Yu Wang, Hikari Takeshita, Koichi Yamamoto, Yibin Huang, Cheng Wang, Tsuneo Nakajima, Yoichi Nozato, Taku Fujimoto, Serina Yokoyama, Kazuhiro Hongyo, Futoshi Nakagami, Hiroshi Akasaka, Yoichi Takami, Yasushi Takeya, Ken Sugimoto, Hiromi Rakugi
Summary: This study found that Ang II did not affect ACE2 and other molecules associated with SARS-CoV-2 infection, supporting recent observational studies suggesting that the use of RASi is not a risk factor for COVID-19.
Article
Medicine, General & Internal
Noelia Diaz-Troyano, Pablo Gabriel-Medina, Stephen Weber, Martin Klammer, Raquel Barquin-DelPino, Laura Castillo-Ribelles, Angels Esteban, Manuel Hernandez-Gonzalez, Roser Ferrer-Costa, Tomas Pumarola, Francisco Rodriguez-Frias
Summary: The predictive value of soluble angiotensin-converting enzyme 2 (sACE2) in predicting hospitalization risk and disease severity in patients with SARS-CoV-2 infection was evaluated. Compared with discharged patients, levels of sACE2 were significantly lower, while levels of CRP, GDF-15, IL-6, and sFlt-1 were significantly higher in hospitalized patients with SARS-CoV-2. sACE2 could be further investigated as a potential biomarker or as part of a panel to predict the severity of COVID-19 and the need for hospitalization.