Allosteric Modulation of Small Molecule Drugs on ACE2 Conformational Change upon Binding to SARS-CoV-2 Spike Protein DOI

Duen‐Shian Wang,

Hamed S. Hayatshahi, Vindi M. Jayasinghe‐Arachchige

et al.

2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Journal Year: 2021, Volume and Issue: unknown, P. 2587 - 2594

Published: Dec. 9, 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a worldwide pandemic (COVID-19). Drug repurposing studies, including drugs such as dexamethasone (DEX), chloroquine (CQ), and telmisartan (TLS), have been performed in COVID-19 clinical trials. DEX CQ demonstrated vitro to bind angiotensin-converting enzyme 2 (ACE2), cellular entry receptor utilized by SARS-CoV-2. However, how DEX/CQ ACE2 their mechanisms of action are still unknown. We that DEX, CQ, TLS disrupt the interactions between SARS-CoV-2 spike protein human via binding an allosteric site close viral region at peptidase domain ACE2, causing conformational change ACE2. defined four states based on two helices distances. Our molecular dynamics simulations suggested shifted conformation populations away from "Open" conformation. Such population shift is further enhanced Delta variant. The rescues this allosterically keep mostly. findings provide potential insight modulating may prevent invasion due unfavored poses for binding.

Language: Английский

Autophagy in health and disease: From molecular mechanisms to therapeutic target DOI Creative Commons
Guang Lu, Yu Wang, Yin Shi

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(3)

Published: July 10, 2022

Macroautophagy/autophagy is an evolutionally conserved catabolic process in which cytosolic contents, such as aggregated proteins, dysfunctional organelle, or invading pathogens, are sequestered by the double-membrane structure termed autophagosome and delivered to lysosome for degradation. Over past two decades, autophagy has been extensively studied, from molecular mechanisms, biological functions, implications various human diseases, development of autophagy-related therapeutics. This review will focus on latest research, covering mechanisms control biogenesis autophagosome-lysosome fusion, upstream regulatory pathways including AMPK MTORC1 pathways. We also provide a systematic discussion implication cancer, neurodegenerative disorders (Alzheimer disease, Parkinson Huntington's Amyotrophic lateral sclerosis), metabolic diseases (obesity diabetes), viral infection especially SARS-Cov-2 COVID-19, cardiovascular (cardiac ischemia/reperfusion cardiomyopathy), aging. Finally, we summarize pharmacological agents that have therapeutic potential clinical applications via targeting pathway. It believed decades hard work research eventually bring real tangible benefits improvement health diseases.

Language: Английский

Citations

73
COVID-19 challenges and its therapeutics DOI Open Access
Sabi Ur Rehman, Shaheed Ur Rehman, Hye Hyun Yoo

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2021, Volume and Issue: 142, P. 112015 - 112015

Published: Aug. 5, 2021

COVID-19, an infectious disease, has emerged as one of the leading causes death worldwide, making it severe public health issues in recent decades. nCoV, novel SARS coronavirus that brought together scientists quest for possible therapeutic and preventive measures. The development new drugs to manage COVID-19 effectively is a challenging time-consuming process, thus encouraging extensive investigation drug repurposing repositioning candidates. Several medications, including remdesivir, hydroxychloroquine, chloroquine, lopinavir, favipiravir, ribavirin, ritonavir, interferons, azithromycin, capivasertib bevacizumab, are currently under clinical trials COVID-19. In addition, several medicinal plants with considerable antiviral activities potential candidates Statistical data show pandemic yet slow down, authorities placing their hopes on vaccines. Within short period, four types vaccines, namely, whole virus, viral vector, protein subunit, nucleic acid (RNA/DNA), which can confer protection against different ways, were already trial. SARS-CoV-2 variants spread associated antibody escape from virus Spike epitopes, grave concerns re-infection even compromises effectiveness Despite these efforts, treatment still solely based management through supportive care. We aim highlight trends relevant statistics, findings, well therapeutics, in-line methods, measures, vaccines combat prevalence

Language: Английский

Citations

96
Strategies for the development and approval of COVID-19 vaccines and therapeutics in the post-pandemic period DOI Creative Commons
Danyi Ao, Xuemei He, Jian Liu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 21, 2023

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant casualties and put immense strain on public health systems worldwide, leading to economic recession social unrest. In response, various prevention control strategies have been implemented globally, including vaccine drug development the promotion preventive measures. Implementing these effectively curbed transmission virus, reduced infection rates, gradually restored normal activities. However, mutations SARS-CoV-2 led inevitable infections reinfections, number deaths continues rise. Therefore, there is still a need improve existing strategies, mainly focusing developing novel vaccines drugs, expediting medical authorization processes, keeping epidemic surveillance. These measures are crucial combat Coronavirus disease (COVID-19) pandemic achieve sustained, long-term prevention, management, control. Here, we summarized characteristics COVID-19 drugs suggested potential future directions for their development. Furthermore, discussed COVID-19-related policies over past years presented some future.

Language: Английский

Citations

28
Misinformation on social networks during the novel coronavirus pandemic: a quali-quantitative case study of Brazil DOI Creative Commons
Priscila Biancovilli, Lilla Makszin, Cláudia Jurberg

et al.

BMC Public Health, Journal Year: 2021, Volume and Issue: 21(1)

Published: June 23, 2021

Abstract Background One of the challenges posed by novel coronavirus pandemic is infodemic risk , that is, a huge amount information being published on topic, along with misinformation and rumours; social media, this phenomenon amplified, it goes faster further. Around 100 million people in Brazil (50% inhabitants) are users media networks – almost half country’s population. Most Internet unregulated, its quality remains questionable. Methods In study, we examine main characteristics topic. We analysed 232 pieces Brazilian fact-checking service “Agência Lupa”. The following aspects each news item were analysed: a) what has circulated?; b) What content classification, sentiment type misinformation?; d) Are there recurrent themes sample studied? Results Facebook (76%), followed WhatsApp, 10% total cases. Half stories (47%) classified as “real-life”, focus everyday situations, or circumstances involving people. Regarding misinformation, preponderance fabricated content, 53% total, false context (34%) misleading (13%). Wrong was mostly text format (47%). found 92.9% “fabricated content” “health tips”, 88.9% “virtual scams” also fabricated. Conclusion science communicators must understand about COVID-19, so they can develop attractive, up-to-date evidence-based helps to increase health literacy counteract spread information.

Language: Английский

Citations

42
The Effect of COVID-19 on NF-κB and Neurological Manifestations of Disease DOI Creative Commons
Don A. Davies,

Aida Adlimoghaddam,

Benedict C. Albensi

et al.

Molecular Neurobiology, Journal Year: 2021, Volume and Issue: 58(8), P. 4178 - 4187

Published: June 1, 2021

Language: Английский

Citations

41
The potential role of SARS‐CoV‐2 infection in acute coronary syndrome and type 2 myocardial infarction (T2MI): Intertwining spread DOI Creative Commons
Aseel Awad Alsaidan, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Immunity Inflammation and Disease, Journal Year: 2023, Volume and Issue: 11(3)

Published: March 1, 2023

Abstract Coronavirus disease 2019 (COVID‐19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has been shown that SARS‐CoV‐2 infection‐induced inflammatory and oxidative stress associated endothelial dysfunction may lead to the development of coronary (ACS). Therefore, this review aimed ascertain link between infection ACS. ACS spectrum myocardial ischemia due sudden decrease in blood flow, ranging from unstable angina infarction (MI). Primary or type 1 MI (T1MI) mainly plaque rupture and/or erosion with subsequent occlusive thrombosis. Secondary (T2MI) cardiac systemic disorders without atherothrombotic disruption. Acute linked nonobstructive such as vasospasm, dilated cardiomyopathy, fibrosis, myocarditis. Furthermore, inflammation might affect atherosclerotic stability through augmentation preload afterload. Nevertheless, major vessels plaques develop minor during COVID‐19 since arteries are not initially primarily targeted low expression angiotensin‐converting enzyme vessels. In conclusion, hypercytokinemia, direct cardiomyocyte injury, dysregulation renin‐angiotensin system aggravate underlying cause new‐onset T2MI. As well, arrhythmias induced anti‐COVID‐19 medications could worsen

Language: Английский

Citations

15
Friend or Foe? Implication of the autophagy-lysosome pathway in SARS-CoV-2 infection and COVID-19 DOI Creative Commons
Weifeng He, Yuan Gao, Jing Zhou

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(12), P. 4690 - 4703

Published: Jan. 1, 2022

There is increasing amount of evidence indicating the close interplays between replication cycle SARS-CoV-2 and autophagy-lysosome pathway in host cells. While autophagy machinery known to either assist or inhibit viral process, reciprocal effects on have also been increasingly appreciated. More importantly, despite disappointing results from clinical trials chloroquine hydroxychloroquine treatment COVID-19, there still ongoing effort discovering new therapeutics targeting pathway. In this review, we provide an update-to-date summary cells pathogen at molecular level, highlight prognostic value markers COVID-19 patients discuss potential developing novel therapeutic strategies for by Thus, understanding nature such interactions expected battling against global pandemic.

Language: Английский

Citations

23
Alveolar macrophage endosomal-lysosomal system: potential therapeutic targets for COVID-19 DOI Creative Commons
Yungang Lan, Gaili Wang, Zhenzhen Wang

et al.

Animals and zoonoses., Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Cinchona Plantation in the Eastern Himalayas and Its Potential in Prevention and Treatment of COVID-19 and Other Viral Diseases DOI
Sayan Bhattacharya, Prabhakar Sharma

Published: Jan. 1, 2025

Language: Английский

Citations

0
pH-dependent endocytosis mechanisms for influenza A and SARS-coronavirus DOI Creative Commons
Amar Aganović

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

The ongoing SARS-CoV-2 pandemic and the influenza epidemics have revived interest in understanding how these highly contagious enveloped viruses respond to alterations physicochemical properties of their microenvironment. By mechanisms conditions by which exploit pH environment host cell during endocytosis, we can gain a better they pH-regulated anti-viral therapies but also pH-induced changes extracellular environments. This review provides detailed explanation pH-dependent viral structural preceding initiating disassembly endocytosis for A (IAV) SARS coronaviruses. Drawing upon extensive literature from last few decades latest research, I analyze compare circumstances IAV SARS-coronavirus undertake endocytotic pathways that are pH-dependent. While there similarities patterns leading fusion, activation differ. In terms fusion activity, measured values IAV, across all subtypes species, vary between approximately 5.0 6.0, while necessitates lower 6.0 or less. main difference endocytic is SARS-coronavirus, unlike require presence specific pH-sensitive enzymes (cathepsin L) endosomal transport. Conversely, conformational virus under acidic endosomes occur due envelope glycoprotein residues protein ion channels (viroporins) getting protonated H+ ions. Despite research over several decades, comprehending pH-triggered still poses significant challenge. precise protonation certain transport both remain incompletely understood. absence evidence, further needed.

Language: Английский

Citations

9