Coronavirus Outbreak (COVID-19) Explained

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Where did the coronavirus come from?
How does COVID-19 work?
What are the treatments?
How can I test if I am immune?

I’m thankful that people are educating themselves on epidemiology and virology. Important biological discussions are happening in our homes and with our families. The biotechnology, pharmaceutical, and vaccine industries are preparing for defense against such viruses as SARS-CoV2 and influenza. To give a sense of the severity of our collective predicament, the last time the Church of the Holy Sepulcher in Jerusalem closed was in 1349 during the “black plague.” As of March 31st, there are over 850,000 confirmed cases and 40,000 deaths in 180 countries (Worldometer). We must persevere by advancing our science and medicine.

Where did the coronavirus come from?

Here’s what we know. The first infections were linked to a live animal market in Wuhan, China (CDC, 2020). Some viruses, for example, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), are known to have infected animals and then jumped to humans. As to the culpable species for COVID-19, some scientists have accused pangolins, scaly anteaters, while researchers at the Wuhan Institute of Virology have suggested that the virus is of probable bat origin (Liu, P et al., 2019, Zhou, P et al., 2020). A virus could potentially be engineered through directed evolution techniques to mimic the natural process; although, a recent study by Scripps Research Institute found no evidence of laboratory manipulation (Andersen, K et al., 2020). At present, hundreds of universities and laboratories worldwide are collecting samples of COVID-19 (1,500 so far), sequencing their genomes, and uploading them onto an open-source platform called Nextstrain. 8 strains of coronavirus have been identified that are circling the globe (Nextstrain, 2020).

How does COVID-19 work?

The structure of SARS-CoV2 consists of spike proteins which make up the distinct spikes on the viral surface and facilitate binding to the host cell receptors (Cascella, M et al., 2020). Along with hemagglutinin-esterase dimers (HE), viruses enter cells through a process of receptor-mediated endocytosis. Specifically, the spike glycoprotein homotrimers complex with host cell angiotensin-converting enzyme 2 (ACE2) receptors (Song, W et al., 2018). Other structural elements include the nucleocapsid proteins (N), envelope proteins (E), and membrane proteins (M), which contribute to functions that may impact virus pathogenicity. The virus also contains its RNA genome. Once the host is infected, the virus may produce an excessive immune reaction or “cytokine storm” leading to tissue damage and pneumonia (Mehta, P et al., 2020). Interleukin 6 (IL-6) proteins produced by activated leukocytes may be the culprit of such a pro-inflammatory storm. Patients initially present with fever, dry cough, and dyspnea (Guo, YR et al., 2020). The clinical spectrum for COVID-19 varies from conditions characterized by respiratory failure to systemic manifestations of sepsis, septic shock, and multiple organ dysfunction syndromes (MODS) (Chen, R et al., 2020).

What are the treatments?

There are dozens of companies working on potential vaccines, treatments, and cures for COVID-19. These therapies either work to prevent infection or combat specific mechanisms of disease progression. Companies like Medtronic (MDT), ResMed, (RMD) General Electric (GE), and Allied Healthcare Products (AHPI), manufacturers of respiratory care devices, have responded to the increased demand for ventilators. On the 20th of March, Bellerophon’s (BLPH) gas therapy (INOpulse) was approved by the FDA, which caused the stock price to rise over 550% in premarket trading (FierceBiotech, 2020). This treatment involves inhaled nitric oxide, which acts a vasodilator thereby relaxing the lung muscles and blood vessels. The nitric oxide blocks the replication of SARS-CoV2 and improves survival of infected cells.  In drug development, one approach is to reduce the activity of ACE2 receptors, which would limit the ability of SARS-CoV2 to penetrate cells. Currently developed ACE1 inhibitors used to treat hypertension and heart failure do not inhibit ACE2. A similar approach involves giving soluble recombinant human ACE2 protein to limit coronavirus attachment to cell membranes, cell entry, and replication. There are also both DNA and RNA strategies for vaccines. In a recent publication, researchers at Stanford have proposed a gene editing strategy using CRISPR-Cas13 or “PAC-MAN” (Prophylactic Antiviral CRISPR in huMAN cells) (Abbot, T et al., 2020). CRISPR RNAs (crRNAs) were developed to target conserved viral regions and cleave SARS-CoV2. While gene editing is one vein of research, there are many pharmaceutical companies involved with developing other coronavirus drugs and vaccines.

Here is a list of other treatments:

  • Chloroquine approved for emergency use by US FDA
  • Favilavir, the first approved coronavirus drug in China

Novel coronavirus vaccines:

  • Fusogenix DNA vaccine by Entos Pharmaceuticals
  • ChAdOx1 nCoV-19 by University of Oxford
  • Gimsilumab by Roivant Sciences
  • AdCOVID by Altimmune
  • TJM2 by I-Mab Biopharma
  • Coronavirus vaccine by Medicago
  • AT-100 by Airway Therapeutics
  • TZLS-501 by Tiziana Life Sciences
  • OYA1 by OyaGen
  • BPI-002 by BeyondSpring
  • Altimmune’s intranasal coronavirus vaccine
  • INO-4800 by Inovio Pharmaceuticals and Beijing Advaccine Biotechnology
  • NP-120 (Ifenprodil) by Algernon Pharmaceuticals
  • APN01 by University of British Columbia and APEIRON Biologics
  • mRNA-1273 vaccine by Moderna and Vaccine Research Center
  • Avian Coronavirus Infectious Bronchitis Virus (IBV) vaccine by MIGAL Research Institute
  • TNX-1800 by Tonix Pharmaceuticals
  • Brilacidin by Innovation Pharmaceuticals
  • Recombinant subunit vaccine by Clover Biopharmaceuticals
  • Vaxart’s coronavirus vaccine
  • CytoDyn-leronlimab
  • Linear DNA Vaccine by Applied DNA Sciences and Takis Biotech
  • BXT-25 by BIOXYTRAN to treat late-stage acute respiratory distress syndrome (ARDS)
  • MERS CoV vaccines for coronavirus
  • Novavax’s MERS coronavirus vaccine candidate
  • Inovio Pharma’s INO-4700

Coronavirus drugs:

  • Remdesivir (GS-5734) by Gilead Sciences
  • Actemra by Roche to treat coronavirus-related complications
  • Biocryst Pharma’s Galidesivir, a potential antiviral for coronavirus treatment
  • Regeneron’s REGN3048-3051 and Kevzara
  • SNG001 by Synairgen Research
  • AmnioBoost by Lattice Biologics
  • Amgen and Adaptive Biotechnologies antibody therapy
  • Vir Biotechnology and Alnylam Pharmaceuticals RNAi targeting ACE2 and TMPRSS2

Other companies developing coronavirus vaccines/drugs:

  • Enanta Pharmaceuticals
  • Predictive Oncology
  • Emergent BioSolutions
  • Integral Molecular
  • AJ Vaccines
  • Takeda Pharmaceutical Company
  • Heat Biologics
  • Pfizer
  • Mateon Therapeutics
  • Hong Kong University of Science and Technology
  • Vaccine by Generex
  • Coronavirus drugs by Columbia University
  • Vaccine by Tulane University
  • Coronavirus vaccine by ImmunoPrecise Antibodies
  • Serum Institute of India
  • Southwest Research Institute
  • Zydus Cadila
  • NanoViricides
  • Vir Biotechnology

How can I test if I am immune?

COVID-19 test kits can be used to predict how the disease will affect the world. PCR-based tests are useful for the newly infected and for detecting virus. However, to identify those who have already been infected and possess immunity, a test is needed to detect antibodies generated in response to infection of COVID-19. Antibody tests can help to determine who has immunity. These tests are high in demand and are becoming more widely available. The more people we can test positive for immunity, the sooner we can resume work and normal life.