COVID-19: Challenges and Potential Solutions

EriVan Bio

The coronavirus disease 2019 (COVID-19) outbreak originating in Wuhan, China has spread to more than 190 countries so far. It has infected 3 million individuals of all ages as of May 2020. The global death toll has peaked at 200,000 which is expected to further rise in the coming weeks. Although most cases exhibit mild to moderate symptoms (including fever, upper respiratory tract symptoms, shortness of breath, and digestive track symptoms), severe cases can lead to pneumonia, multiple organ dysfunction syndrome (MODS), and death. The pandemic is posing a significant global health and economic threat, and COVID-19 has drawn unprecedented attention from the public. The economic and financial impacts are evolving further during the crisis.

Coronaviruses (Coronaviridae e.g. SARS-CoV, SARS-CoV-2, HCoV NL63, HKU1, and MERS-CoV) are spherical, nano-sized particles with a diameter around 120 nm. These viruses consist of an envelope (about 80 nm) and spikes (about 20 nm) that project outward. The viral envelope of the viruses consists of a lipid bilayer where the membrane, envelope, and spike proteins are anchored. Inside the envelope is the nucleocapsid, which contains the positive-sense single-stranded RNA genome in complex with the nucleocapsid proteins. COVID-19 shares symptoms of viral pneumonia; severe cases arise in individuals having underlying illnesses, and often die of multiple organ dysfunction syndrome (MODS). Once MODS reaches advanced stages, mortality is estimated to be as high as 90%. Therefore, there is a clear need to establish well-defined diagnostic and preventive strategies for patients with severe COVID-19 infection at risk of MODS. For such an important mission, clinical and preclinical research must explain many underlying mechanisms of the clinical presentations of MODS in COVID-19 patients.

The economic impact of the pandemic is still evolving. The current stock market downturn and the increasing unemployment rate paints a grim picture for the future. The oil price war, mandatory lockdowns and worldwide travel bans caused the stock markets to experience their worst day since 1987, and corporate valuations fell approximately 30% below their midterm highs. COVID-19 turns out to be an utterly unprecedented type of pandemic crisis. It poses disproportionate public health risk to different age groups. However, the global economic impacts do not correlate well with the actual health outcomes when compared to other similar infections such as flu. Consequently, a global recession is probably on its emergence. Different scenarios depict unequal impacts on the GDP growth rates. Some predict that national GDPs receive a hit of 3-5% depending on the subject country and how the pandemic is managed. The health and economic outcomes will heavily depend on the preventative measures against the pandemic, government policies to support SMEs and families under financial distress, and to control unemployment crises.

One of the prospective reliefs will be developing medicines or an effective vaccine against the virus. However, this not a novel challenge to humankind. There are very few curative drugs against viruses that cause morbidity and mortality in humans. Therefore, novel approaches are required in this battle. The development of a safe preventative or therapeutic modality is expected to have a major impact on the COVID-19 pandemic. EriVan Bio has been investigating extracellular vesicles, which are a heterogeneous population of naturally existing nano- and micro-sized vesicles, including microvesicles and exosomes. The exosomes are described as nanoparticles of 30–150 nm size which originate from cellular endosomes and are secreted through the exocytosis pathway. As large amounts of EVs are required for both preclinical and clinical development, methods to manufacture and purify EVs from different sources is vital to move the field forward. EriVan Bio has developed a robust and scalable manufacturing process to produce exosomes and secretome (that includes growth factors, proteins and cytokines) from different sources including human stem cells.

EriVan Bio has been looking into the application of exosomes and secretome to prevent and treat COVID-19 infection. Here is EriVan Bio’s approach to treating COVID-19:

  • The inhibition of the virus-binding-receptors (e.g. host cell ACE2 receptors) may block the viral endocytosis. However, caution should also be considered when blocking the physiological routes of cells. The entry and infectious capability of viruses into host cells can be blocked by treating the virus with a decoy particle resembling a cell, so that the virus binds partially to the decoy particle instead of target cells. We propose that extracellular vesicles (EVs) might be an excellent virus-decoy since (a) they have the same membrane structure as their parental cells, (b) surface proteins/receptors expressed by a cell are usually also found on the EVs, and (c) it is possible to overexpress a specific surface protein (e.g. ACE2 receptors) on EVs.
  • Stem cell exosomes and secretome deliver the regenerative and immunomodulatory properties of the stem cells while they are not replicative and do not differentiate in the body. Therefore, safe stem cell exosome-based therapeutics are expected to have a major impact on the treatment of the degeneration and tissue damage following COVID-19 infection. EriVan Bio develops candidates to restore lung function in patients suffering from long-term pulmonary damage they sustained after recovery from the COVID-19 interstitial pneumonia and acute respiratory distress syndrome (ARDS).

Remarks
COVID-19 has emerged as a great global challenge in the past few months and is leaving high mortality in almost all countries. The pandemic may not be completely taken under control unless there are safe and effective treatments. EriVan Bio looks into the development of exosome-based modalities to prevent and treat COVID-19 as well as restoring lung function in the survivors.

References
Available upon request.

EriVan Bio LLC
erivanbio.com
12085 Research Drive, Lab 180
Alachua, Fl 32615
Tel: +1 407 580 1376

Disclaimer. The information provided in this White Paper is strictly the perspectives and opinions of EriVan Bio LLC and does not represent any specific project or product. No information in this white paper should be considered or construed to be business or technical advice or directions. The information shared in this whitepaper is not all-encompassing or comprehensive and does not in any way intend to create or put into implicit effect binding terms and conditions.