{"id":3446,"date":"2020-04-20T13:02:52","date_gmt":"2020-04-20T13:02:52","guid":{"rendered":"https:\/\/www.editage.com\/insights\/covid-19-ongoing-coronavirus-research-and-vaccine-development\/"},"modified":"2025-01-15T06:30:12","modified_gmt":"2025-01-15T06:30:12","slug":"covid-19-ongoing-coronavirus-research-and-vaccine-development","status":"publish","type":"post","link":"https:\/\/www.editage.com\/insights\/covid-19-ongoing-coronavirus-research-and-vaccine-development","title":{"rendered":"COVID-19: Ongoing coronavirus research and vaccine development"},"content":{"rendered":"

Editor\u2019s note:<\/u><\/i><\/b>\u00a0This article was\u00a0originally published on Kolabtree<\/a><\/span><\/span>\u00a0and has been republished here with permission. The author, Mahasweta Pal, is medical editor with Cactus Communications. Founded in 2015,\u00a0Kolabtree<\/a><\/u>\u00a0helps organizations hire freelance scientists and researchers from across the globe.<\/i><\/span><\/span><\/span><\/p>\n

The Director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci, currently leading the United States\u2019 coronavirus response team,\u00a0stated that COVID-19 will not be limited<\/a><\/span><\/span>\u00a0to the present outbreak and hinted at the virus\u2019 capability to occur as a potential seasonal problem. His press address at the White House on 24th<\/sup> March placed immense significance on the development of a vaccine and if possible, new drugs to treat moderately severe cases of the disease. This week, the\u00a0number of deaths<\/a><\/span><\/span>\u00a0neared 50,000 globally with Italy, Spain, and the United States recording 27000+ deaths (24th<\/sup> March). Needless to say, the need for more robust healthcare R&D has never been higher. The murkiness in the current situation is multifactorial, as the importation of drugs from other countries including China was halted and the availability of ventilators diminishes.<\/span><\/span><\/span><\/p>\n

Amidst the lockdowns or industrial shutdowns to curtail the contagion, the academic community and healthcare researchers have been pulling in available resources together to meet the ever-rising demand for vaccines, medications, diagnostic kits, personal protective equipment, and other epidemic-fighting requirements. Here, I list some of the key developments that occurred in the past months to counteract the COVID-19 pandemic.<\/span><\/span><\/span><\/p>\n

COVID-19 research: Molecular biology & pathogenesis<\/b><\/span><\/span><\/span><\/p>\n

Since the upbeat chatter about the coronavirus emerged in December last year, the novel coronavirus (SARS-CoV-2) has been the epicenter of scientific research whilst wreaking havoc in more than 190 countries. Its origin was speculated to be\u00a0from bats<\/a><\/span><\/span>\u00a0and more recently, from a rare mammalian species\u00a0called pangolins<\/a><\/span><\/span>\u00a0in China. The pathogen causing COVID-19 is the seventh coronavirus that infected humans, after\u00a0HCoV\u2010OC43, HCoV\u2010229E<\/a><\/span><\/span>, HCoV\u2010NL63, HCoV\u2010HKU1, MERS-CoV, and SARS-CoV, of which the first 4 are associated with mild respiratory distress\/infections while the last two have caused epidemics in\u00a0Middle-Eastern Asia<\/a><\/span><\/span>\u00a0and Asia, Europe,\u00a0North and South America in\u00a0<\/a><\/span><\/span>the last decades, respectively. Characterized by an enveloped, positive\u2010sense, and single\u2010stranded RNA structure similar to all human-infecting coronaviruses, SARS-CoV-2 shares an almost similar lifecycle as SARS-CoV using the angiotensin-converting enzyme-2 (ACE2) receptor for entering human cells.<\/span><\/span><\/span><\/p>\n

The\u00a0lifecycle of SARS-CoV-2<\/a><\/span><\/span>\u00a0starts when the S protein is adjacent to the host cell\u2019s ACE2 receptor. This enveloped spike-like (S) protein represents the virus\u2019 most alarming, determinant feature that governs its pathogenicity; the S protein is composed of 2 domains S1 and S2 that enable the viral body to bind to the ACE2 receptor and fuse with the cell membrane. This S protein\u00a0is densely glycosylated<\/a><\/span><\/span>\u00a0and has a 10 to 20-fold higher affinity for the ACE2 receptor than SARS-CoV. The cell-membrane fusion between the host cell ACE2 receptor and S protein involves significant structural rearrangements to establish a stable post-fusion conformation, which is followed by viral RNA replication, transcription, and creation of a viral-protein rich genome. The viral proteins then enable the transmission of virions through the vesicles of the endoplasmic reticulum-Golgi complex (ERGIC).<\/span><\/span><\/span><\/p>\n

The mechanism of SARS-COV-2 transmission thus highlights the high-risk group primarily comprising\u00a0cardiovascular disease patients<\/a><\/span><\/span>\u00a0on ACE2 inhibitor and angiotensin receptor blocker (ARB) medications, because these medications mediate the creation of a large pool of ACE2 receptors in the circulatory frameworks. Another significant insight is that the S protein is being used as the target for potential vaccines, antibodies, monoclonal antibodies, and pharmaceutical treatments. Ongoing research aims to answer key questions regarding the variety of pathogenic strains of SARS-COV-2, its genetic similarities with other enveloped, single-stranded viruses, and the mutational abilities of its receptor-binding domains.<\/span><\/span><\/span><\/p>\n

Preclinical and clinical testing of repurposed drugs<\/b><\/span><\/span><\/span><\/p>\n

Currently, healthcare workers are utilizing crucial anti-malaria medications such as hydroxychloroquine and chloroquine to treat mild to moderate COVID-19 cases. However, the pandemic task forces have some reasons for cheer as Gilead Sciences and Roche leading phase III trials on anti-SARS-CoV-2 treatments with anti-HIV, anti-malarial, and against the SARS-Cov-2 pathogenesis.<\/span><\/span><\/span><\/p>\n

1. Gilead Sciences<\/b><\/span><\/span><\/span><\/p>\n

Gilead Sciences, a company with a large portfolio of antiviral therapies, reported early data on Remdesivir, which failed to show efficacy against Ebola previously but\u00a0showed promising activity against SARS-Cov-2<\/a><\/span><\/span>. Currently, 5 trials in the European Union are testing the safety and antiviral activity of remdesivir, apart from the SOLIDARITY 4-treatment Trial conducted by the World Health Organization (ISRCTN83971151<\/a><\/span><\/span>). The main outcome measures of the SOLIDARITY trial include reducing the\u00a0need for ventilation in severe cases and preventing mortality<\/a><\/span><\/span>.<\/span><\/span><\/span><\/p>\n

Three of Gilead\u2019s self-sponsored\u00a0clinical trials<\/a><\/span><\/span>\u00a0on Remdesivir are underway in multiple European countries, while the\u00a0Discovery trial in France<\/a><\/span><\/span>\u00a0tested 4 treatment combinations based on Standard of care versus remdesivir, lopinavir\/ritonavir, Hydroxychloroquine and lopinavir\/ritonavir (anti-HIV protease inhibitors) and interferon-\u03b2. This\u00a0trial<\/a><\/span><\/span>\u00a0reported the\u00a0superior activity of HCQ+LOP\/RIT<\/a><\/span><\/span>\u00a0in a 28-day period. The promising early results of Remdesivir\u2019s activity lead to more expanded testing by the\u00a0US government<\/a><\/span><\/span>\u00a0(2 multi-center trials) with main outcomes monitored over a preliminary 15-day period since March 20, 2020. The COVID-Tox trial by Gilead is focusing on Remdeisvir\u2019s effects of reducing the rate of\u00a0renal failure and heart failure<\/a><\/span><\/span>-induced fatalities.<\/span><\/span><\/span><\/p>\n

2. Roche<\/b><\/span><\/span><\/span><\/p>\n

Roche has started trials in Italy and France where the infection rates surged in March. The investigators are placing their bets on Tocilizumab, an approved treatment for rheumatoid arthritis and cytokine response syndrome (CRS) since the\u00a0Lancet\u00a0<\/a><\/i>reported that severe COVID-19 patients developed CRS<\/a><\/span><\/span>\u00a0after hospitalization, which can lead to mortality. Tocilizumab is also under\u00a0trials<\/a><\/span><\/span>\u00a0with Favipiravir, a new\u00a0anti-flu drug that showed reasonable effectiveness<\/a><\/span><\/span>\u00a0in clinical trials conducted in China.<\/span><\/span><\/span><\/p>\n

3. AbbVie<\/b><\/span><\/span><\/span><\/p>\n

AbbVie\u2019s anti-HIV agents, namely Lopinavir and Ritonavir were debated among scientists regarding their efficacy. While a\u00a0small sample study in China failed to show<\/a><\/span><\/span>\u00a0effectiveness against SARS-CoV-2, this combination of RNA-protease inhibitors remains well-established as effective against previous strains of coronaviruses, namely MERS-CoV and SARS-CoV. Thereafter, the World Health Organization\u00a0announced the launch of the SOLIDARITY trial<\/a><\/span><\/span>, wherein Gilead\u2019s Remdesivir, hydroxychloroquine and chloroquine, Lopinavir\/Ritonavir plus interferon-\u03b2 will be tested on a global cohort, including Canada, France, Spain, Norway, Russia, and Switzerland. Earlier, the promising Lopinavir\/Ritonavir combination was tested aggressively in China, South Korea, and Hong Kong in combination with Ribavirin, interferon-\u03b2, and a\u00a0fixed-dose combination anti-HIV drug \u2018Genvoya\u2019<\/a><\/span><\/span>. Genvoya is a cocktail containing cobicistat, elvitegravir, emtricitabine, and tenofovir, which was tested in combination with Ritonavir to observe whether treatment without supplemental oxygenation and ICU admissions was possible as the shortages of ventilators and ICUs reached unprecedented levels. Ascletis Pharma, the Chinese company that manufactured Genvoya\u00a0reported last month<\/a><\/span><\/span>\u00a0that in this Phase IV trial comprising 11 COVID-19 patients, 10 had been discharged with moderately controlled symptoms and deemed as disease-free over a 30-day period.<\/span><\/span><\/span><\/p>\n

4. Sanofi and\u00a0Regeneron<\/b><\/span><\/span><\/span><\/p>\n

Sanofi and Regeneron are conducting a\u00a0Phase II\/III trial<\/a><\/span><\/span>\u00a0enrolling severely infected COVID-19 patients for testing Sarilumab, an interleukin-6 receptor inhibitor that showed anti-inflammatory responses against severe COVID-19. The trial is underway in Italy, Spain, Germany, France, Canada, Russia, and the United States, which have been massively impacted by the pandemic. Sarilumab is expected to show efficacy in ameliorating the severe acute respiratory distress syndrome associated with COVID-19 and its associated life-threatening complications. The trial is testing whether one intravenous dose can prevent fatalities, reduce the viral load, fever, and control the need for oxygenation in severe cases of the disease over 15-day periods. Other trials by the\u00a0University of California Davis<\/a><\/span><\/span>\u00a0and the\u00a0University of Chicago<\/a><\/span><\/span>\u00a0are conducting trials to test if sarilumab with Remdesivir is effective in preventing the need for ventilation in severe cases of COVID-19 and to check the efficacy of different doses of sarilumab, respectively.<\/span><\/span><\/span><\/p>\n

5. CDC<\/b><\/span><\/span><\/span><\/p>\n

The CDC has stated that to date, hydroxychloroquine and chloroquine, which are approved for treating malaria and few inflammatory diseases, were able to show strong anti-SARS-CoV-2 activity in a\u00a0Chinese cohort<\/a><\/span><\/span>, especially when combined with azithromycin for treating mild to moderate cases in almost all countries affected by the pandemic. In addition, various approved treatments including corticosteroids and non-steroidal anti-inflammatory drugs, are\u00a0listed<\/a><\/span><\/span>\u00a0to have significant clinical potentials against SARS-CoV-2 such as\u00a0methylprednisolone per WHO\u2019s list of off-label<\/a><\/span><\/span>\u00a0treatments under trial.\u00a0One trial in Belgium<\/a><\/span><\/span>\u00a0is investigating the activity of sargramostim (an immunomodulatory drug) for improving oxygenation and outcomes in COVID-19 complicated with acute hypoxic respiratory failure.<\/span><\/span><\/span><\/p>\n

Novel treatments for COVID-19<\/b><\/span><\/span><\/span><\/p>\n

At least 50 biopharma companies have grabbed a spot in the drug development and discovery landscape including Takeda, Eli Lilly, and Regeneron. The pandemic has spurred a bandwagon of key collaborations in North America, Europe, and Asia, which range from viral gene manipulation, B-cell therapies, viral-neutralizing antibody platforms, and also led to amendments in existing collaborations to accommodate new vaccine\/treatment discovery.<\/span><\/span><\/span><\/p>\n