INDUSTRY: HEALTH/BIOPHARMACEUTICALS 

InvivoSciences, Inc. www.invivosciences.com, Ayla Annac CEO/President

Disease Modeling of Acute Heart Failure Infected by SARS-CoV-2 

A significant increase in heart failure markers, including high-sensitivity cardiac troponin I and D-dimer, separated non-survivors from survivors affected by coronavirus disease 2019 (COVID-19) in Wuhan China (Zhou, Yu et al.). A genomic analysis of SARS-CoV-2 causing COVID-19 confirmed that SARS-CoV-2 could strongly bind to Angiotensin-Converting Enzyme 2 (ACE2) (Andersen, Rambaut, et al. 2020) and promote the viral entry into cells (Hoffmann, Kleine-Weber, et al.). Heart muscle and some other organs profoundly express ACE2. While in a healthy heart, ACE2 does not play a significant role, patients with hypertension, diabetes, aging, and other cardiovascular diseases, ACE2 seems to play a critical role to moderate their disease progression. Therefore, we hypothesis that SARS-CoV-2 infection is dangerous for patients with those underlying conditions. They will die by developing acute heart failure. This hypothesis is supported by the other report showing 16.7% and 7.2% complications are cardiac arrhythmia and acute cardiac injury, respectively (Zheng, Ma et al. 2020).

InvivoSciences, Inc. (IVS) mass-produces human micro heart tissues (NuHeart™) derived from human induced pluripotent stem cells (iPSCs) to provide disease modeling services for pharmaceutical developers. NuHeart™ will be used to develop a disease model of the heart contacted with SARS-CoV-2 (using a non-viral spike protein as a start).  The system will validate the effects of potential treatments to mitigate the deleterious effects of SARS-CoV-2 binding to ACE2. IVS has developed an automated in vitro high-throughput, high-content phenotypic compound screening platform, Live-in-Tissue Analyzer (LITATM), for the assessment of NuHearts™ growing in 96- and 384 well plates. LITA™ measures contractility, action potential (AP), calcium transient (CaT), and mitochondrial activities to analyze the effects of treatment comprehensively.

Reference:

Andersen, K. G., A. Rambaut, W. I. Lipkin, E. C. Holmes, and R. F. Garry (2020). “The proximal origin of SARS-CoV-2.” Nature Medicine.

Hoffmann, M., H. Kleine-Weber, S. Schroeder, N. Krüger, T. Herrler, S. Erichsen, T. S. Schiergens, G. Herrler, N.-H. Wu, A. Nitsche, M. A. Müller, C. Drosten and S. Pöhlmann “SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor.” Cell.

Zheng, Y.-Y., Y.-T. Ma, J.-Y. Zhang and X. Xie (2020). “COVID-19 and the cardiovascular system.” Nature Reviews Cardiology.

Zhou, F., T. Yu, R. Du, G. Fan, Y. Liu, Z. Liu, J. Xiang, Y. Wang, B. Song, X. Gu, L. Guan, Y. Wei, H. Li, X. Wu, J. Xu, S. Tu, Y. Zhang, H. Chen and B. Cao “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.” The Lancet.