Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial

Lobo, Suzana Margareth; Plantefève, Gaétan; Nair, Girish; Joaquim Cavalcante, Adilson; Franzin de Moraes, Nara; Nunes, Estevao; Barnum, Otis; Berdun Stadnik, Claudio Marcel; Lima, Maria Patelli; Lins, Muriel; Hajjar, Ludhmila Abrahao; Lipinski, Christopher; Islam, Shaheen; Ramos, Fabiano; Simon, Tiago; Martinot, Jean-Benoît; Guimard, Thomas; Desclaux, Arnaud; Lioger, Bertrand; Neuenschwander, Fernando Carvalho; DeSouza Paolino, Bruno; Amin, Alpesh; Acosta, Samuel Amil; Dilling, Daniel Forde; Cartagena, Edgardo; Snyder, Brian; Devaud, Edouard; Barreto Berselli Marinho, Ana Karolina; Tanni, Suzana; Milhomem Beato, Patricia Medeiros; De Wit, Stephan; Selvan, Vani; Gray, Jeffrey; Fernandez, Ricardo; Pourcher, Valérie; Maddox, Lee; Kay, Richard; Azbekyan, Anait; Chabane, Mounia; Tourette, Cendrine; Esmeraldino, Luis Everton; Dilda, Pierre J.; Lafont, René; Mariani, Jean; Camelo, Serge; Rabut, Sandrine; Agus, Samuel; Veillet, Stanislas; Dioh, Waly; van Maanen, Rob; Morelot-Panzini, Capucine

doi:10.1016/j.eclinm.2023.102383

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Moreover, the COVA trial revealed that 20-hydroxyecdysone (BIO101) demonstrated statistically significant efficacy, showing a 43.8% reduction in the risk of death or respiratory failure (p = 0.0426), with nine patients needing treatment. The results confirm BIO101 ′ s good safety profile and support its clinical relevance in modulating the renin-angiotensin system through MASR activation for treating COVID-19 [113,114]. These findings indicate the need for further investigation of BIO101 as a potential treatment for hospitalised patients with severe pneumonia due to COVID-19 [113].…”

Section: Advancements In Sars-supporting

confidence: 68%

Unravelling Insights into the Evolution and Management of SARS-CoV-2

Mushebenge,

Ugbaja,

Mbatha

et al. 2024

BioMedInformatics

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Worldwide, the COVID-19 pandemic, caused by the brand-new coronavirus SARS-CoV-2, has claimed a sizable number of lives. The virus’ rapid spread and impact on every facet of human existence necessitate a continuous and dynamic examination of its biology and management. Despite this urgency, COVID-19 does not currently have any particular antiviral treatments. As a result, scientists are concentrating on repurposing existing antiviral medications or creating brand-new ones. This comprehensive review seeks to provide an in-depth exploration of our current understanding of SARS-CoV-2, starting with an analysis of its prevalence, pathology, and evolutionary trends. In doing so, the review aims to clarify the complex network of factors that have contributed to the varying case fatality rates observed in different geographic areas. In this work, we explore the complex world of SARS-CoV-2 mutations and their implications for vaccine efficacy and therapeutic interventions. The dynamic viral landscape of the pandemic poses a significant challenge, leading scientists to investigate the genetic foundations of the virus and the mechanisms underlying these genetic alterations. Numerous hypotheses have been proposed as the pandemic has developed, covering various subjects like the selection pressures driving mutation, the possibility of vaccine escape, and the consequences for clinical therapy. Furthermore, this review will shed light on current clinical trials investigating novel medicines and vaccine development, including the promising field of drug repurposing, providing a window into the changing field of treatment approaches. This study provides a comprehensive understanding of the virus by compiling the huge and evolving body of knowledge on SARS-CoV-2, highlighting its complexities and implications for public health, and igniting additional investigation into the control of this unprecedented global health disaster.

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Section: Advancements In Sars-supporting

confidence: 68%

Unravelling Insights into the Evolution and Management of SARS-CoV-2

Mushebenge,

Ugbaja,

Mbatha

et al. 2024

BioMedInformatics

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“…54 As reviewed elsewhere, 55,56 interventional studies in human subjects confirm vasodilator actions of Ang-(1-7) in the coronary, splanchnic, and renal circulations. On the other hand, translation of these observational studies to clinical therapy remains elusive although new orally active Ang-(1-7) formulations 57 and Mas agonists 58 are available. Interest in exploring the therapeutic benefit of pharmacological activation of the ACE2/Ang-(1-7)/ Mas axis is reflected in the registration of 372 clinical trials when searching www.clinicaltrials.gov using the term, angiotensin-(1-7).…”

Section: Angiotensin-(1-7)mentioning

confidence: 99%

“…[59][60][61] The outcome of one of these trials using a novel Mas agonist in COVID-19 patients was recently reported and showed the therapeutic efficiency of the drug. 58…”

Section: Angiotensin-(1-7)mentioning

confidence: 99%

Alternative Renin-Angiotensin System

Bader,

Steckelings,

Alenina

et al. 2024

Hypertension

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The renin-angiotensin system is the most important peptide hormone system in the regulation of cardiovascular homeostasis. Its classical arm consists of the enzymes, renin, and angiotensin-converting enzyme, generating angiotensin II from angiotensinogen, which activates its AT 1 receptor, thereby increasing blood pressure, retaining salt and water, and inducing cardiovascular hypertrophy and fibrosis. However, angiotensin II can also activate a second receptor, the AT 2 receptor. Moreover, the removal of the C-terminal phenylalanine from angiotensin II by ACE2 (angiotensin-converting enzyme 2) yields angiotensin-(1-7), and this peptide interacts with its receptor Mas. When the aminoterminal Asp of angiotensin-(1-7) is decarboxylated, alamandine is generated, which activates the Mas-related G-protein-coupled receptor D, MrgD (Mas-related G-protein-coupled receptor type D). Since Mas, MrgD, and the AT 2 receptor have opposing effects to the classical AT 1 receptor, they and the enzymes and peptides activating them are called the alternative or protective arm of the renin-angiotensin system. This review will cover the historical aspects and the current standing of this recent addition to the biology of the renin-angiotensin system.

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