Coronavirus Outbreak (COVID-19) Explained

Video Credit: www.scientificanimations.com

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 20^th 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
• CEL-SCI
• 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.

A single software platform providing automated MS data processing for end-to-end MAM lifecycle management

Alexander Julian Veach¹, Aude Tartiere², Maurizio Bronzetti², Da Ren¹

¹Amgen Inc., Thousand Oaks, CA, United States, ²Genedata, Inc., San Francisco, California, United States

I recently presented this work entitled “A single software platform providing automated MS data processing for end-to-end MAM lifecycle management” at the California Separation Science Society Mass Spectrometry Conference in Chicago, Illinois. Please find the abstract below.

Physiochemical characterization of therapeutic proteins is crucial for product quality control in the biopharmaceutical industry. Robust software that adheres to QbD principles is needed to rapidly identify and quantify multi-attribute method (MAM) LC/MS-based spectra.

Genedata Expressionist provides a single software platform for end-to-end MAM lifecycle management that enables method transfer from early stage molecule assessment to in-process analytics and offers plugins developed for use in GMP release and QC testing environments. The flexibility of the platform enables novel processes to test system suitability, detect new and missing peaks, and overcome limitations in the number of monitored attributes.

Using Genedata Expressionist, we optimized data processing for post-translational modifications (PTMs) including oxidation, deamidation, glycosylation, and clips. We developed methods for calculating relative abundances of PTMs that improved data accuracy by including more peaks, charge states, ion adducts, and peptides with non-specific cleavage. The automated attribute identification and quantification process saved time by avoiding the need for laborious manual integration. Additional time-savings were provided by running Genedata Expressionist on a dedicated server, thereby significantly reducing analysis time for large data sets.

MAM Data Processing Automation with Genedata Expressionist

Alexander Julian Veach¹, Aude Tartiere², Maurizio Bronzetti², Da Ren¹

¹Amgen Inc., Thousand Oaks, CA, United States, ²Genedata, Inc., San Francisco, California, United States

I will be presenting work at upcoming industry symposia. Please find the abstract below.

Physiochemical properties of therapeutic proteins are crucial for product quality control (QC) in the biopharmaceutical industry. Robust and compliant software is needed to rapidly identify and quantify multi-attribute method (MAM) LC/MS-based spectra. For GMP application we assessed ThermoFisher Chromeleon and Genedata Expressionist, which are both 21 CFR Part 11 compliant. Our comparison of these MS data processing software with Amgen’s internal software MassAnalyzer establishes that results from Expressionist are mostly aligned with conventional approaches without significant differences. Due to its readiness to support QC method validation, Expressionist may be a viable fit for end-to-end MAM lifecycle management. The workflows and plugins we create reduce effort during method transfer from early stage molecule assessment to GMP environments. And, we find that Expressionist reduces analysis time for large data sets and provides an accurate orthogonal validation of results. Using a dedicated server, we use a retention time alignment algorithm and merge MS/MS spectra across samples to improve data quality and reduce false positives. Our proposed methods for calculating relative abundance of PTMs such as oxidation, deamidation, glycosylation, and clips increase data accuracy by including more peaks, charge states, adduct ions, and peptides with non-specific cleavage. In Expressionist, manual integration is not necessary as attribute identification and quantification processes are automated. With Expressionist’s flexible system we optimize novel processes to test system suitability, detect new and missing peaks, and generate control charts. Expressionist shows performance benefits in alleviating limitations in the number of attributes monitored and reducing minimum training requirements for a QC analyst. With advanced statistical tools, we present solutions to monitor trends and investigate unexpected results in development and GMP environments employing MAM.

The Role of Data Science in Biotechnology

In the coming years, the integration of the study of data science in the field of biotechnology will have a great impact on present environmental issues, healthcare sectors, and ecological imbalances.

Today, the biotech industry is gaining popularity and it has massive data structures, rich data sources, and efficient storage forms. Companies in various industries have succeeded in solving some serious issues and as a result created profitable gains because of the awareness about the importance of big data and the use of data science techniques. The biotechnology domain does not just consist of big data in terms of DNA information, but it is a rich data source to identify and understand various emerging social, economic, environmental and healthcare problems.  The genetic data of plants, animals and humans is stored in the data banks as to preserve individual identity. Researchers use this massive gene data for research purposes related to various genetic disorders or to analyse and extract meaningful patterns of each gene expression. Researchers tag the certain gene sequence with specific names so that they can track and identify similar bacterial gene sequences from any new gene data. When combined with the genetic information or composition of each person’s lifestyle, health and medicines they take, then it is easy to predict the new person’s health issues and which medicines can be effective based on billions of gene records collected and analysed. Thus, supervised and unsupervised learning algorithms can be applied to understand each individual’s gene data, its relations, similarities and differences when compared with other individual’s gene sequence. By applying data science methodologies to the human genome, we can predict the diseases which are prone to happen. We can solve the mystery – why do some human beings get affected with certain diseases at certain ages? Also we could know – how did they got that infection? When is it likely that they will suffer from a certain type of disease? Which enzymes can cure certain diseases? By analyzing many individual data points we are able to track and control the behavior of each gene sequence during data synthesis and data sequencing, which is useful in order to retrieve any target enzymes. In the human body there are more than 10,000 microbes; with several data science techniques we can predict which microbes might be useful for an individual’s health and a great life.

Personalized healthcare and medication is possible simply with the aids of data science and artificial intelligence. The DNA synthesis work will likely gain high revenues and its operational work will become cheaper than it ever was. Analyzing relationships within various forms of big genetic data sets can achieve new insightful knowledge, solutions to critical problems, and decision making power.

Thus, we will be able to store the world’s digital data about several genes and data storage problems will soon be history. Thus, we can achieve faster computational work in the biotech field. Researchers will focus mainly on optimizing parameters, which can provide the best solution rather than having, for example, an intense focus on just DNA analysis.

Each gene expresses a different function in a living cell. Advances in computational studies will help clarify interactions between foreign and human genes within the body, as well as help to disclose ecological and environmental concerns. Data science and artificial intelligence applications will disrupt the biotechnology industry.