Studies Suggest COVID-19 Could Become Seasonal Virus, Other News

May 29, 2020 | A review of coronavirus immunity studies suggest the COVID-19 virus could become the fifth seasonal coronavirus with recurring epidemics of lessening severity over the next several years. Over 200 SARS-CoV-2 genome sequences have now been completed and released. We round up the week’s research and industry news for COVID-19.

Literature Updates

A new review of findings from over 40 studies on coronavirus immunity, published in the Journal of General Virology, discusses possible implications for the COVID-19 pandemic. The article, written by top U.K. virologists, suggests that SARS-CoV-2 could become the fifth seasonal coronavirus with recurring epidemics of lessening severity over the next several years. For seasonal coronaviruses where disease is mild, there have even been reports of reinfection after as little as 80 days. The authors also discuss the currently available antibody tests for SARS-CoV-2 and explain the differences between these tests, their accuracy and limitations. DOI: 10.1099/jgv.0.001439

In an article published in Chemical & Engineering News, researchers from the Emory Institute for Drug Development report on an emerging antiviral called EIDD-2801 that might turn the tide for this pandemic and the next. It has shown promise against several RNA viruses, including Ebola, influenza and SARS-CoV-1, in cell and animal studies. EIDD-2801 targets the same viral enzyme as remdesivir, but is an oral medication. If shown to be safe and effective, it could be taken at home rather than in the hospital, allowing treatment earlier in the course of the disease. Phase I human trials of EIDD-2801 are now underway in the U.K., and a U.S. trial is slated to begin in the next few weeks. To have an impact, EIDD-2801 will most likely need to be given before the virus has time to ravage the body—ideally, soon after a person is exposed to SARS-CoV-2 or at the initial onset of symptoms. The potential drug's ability to target an array of viruses bodes well for future outbreaks, the authors say. Article.

Researchers in China have used CRISPR/Cas9 gene editing technology to generate a mouse model of infection with SARS-CoV-2 that reproduces human angiotensin-converting enzyme II (hACE2), the receptor that the virus binds to and uses to enter cells in human patients, according to a study that published in Cell Host & Microbe. The mouse model has several advantages over other genetically engineered mice that express hACE2 for modeling SARS-CoV-2 infection, including being precisely inserted into a specific site on the X chromosome and completely replacing the mouse version of the protein. In addition, the model is genetically stable, with few differences among individuals, and the distribution of hACE2 in various tissues better matches that observed in humans. After being infected with SARS-CoV-2 through the nose, the genetically engineered mice showed evidence of robust viral RNA replication in the lung, trachea and brain. The SARS-CoV-2 S protein, which binds to hACE2 to enter host cells, was also present in the lung tissue and brain cells. Additionally, researchers identified Clara cells as the major targets of SARS-CoV-2. The mice developed interstitial pneumonia and older mice had increased production of cytokines. DOI: 10.1016/j.chom.2020.05.020

Researchers at Rovira i Virgili University (URV, Spain) led a study that used computational screening to predict whether any of the 6,466 drugs authorized to treat another pathology could inhibit the main protease (M-pro) of the SARS-CoV-2 virus. The study, which published in the International Journal of Molecular Sciences, demonstrates that a human and a veterinary anti-inflammatory drug—Carprofen and Celecoxib—inhibit a key enzyme in the replication and transcription of the virus. Some of the trials coordinated by the World Health Organization against the COVID-19 pandemic similarly aim to inhibit M-pro using two antiretrovirals such as Lopinavir and Ritonavir (drugs initially designed to treat HIV). The URV study predicted that seven different drugs would inhibit M-pro, but two were selected by the global COVID Moonshot project for in vitro testing. The results obtained show that at a concentration of 50 μM of Celecoxib or Carprofen, the inhibition of the in vitro activity of M-pro is 11.9% and 4%, respectively. Therefore, both molecules could be used as a starting point for further lead optimization to obtain even more potent derivatives. DOI: 10.3390/ijms21113793

Updates from Industry

Airway Therapeutics, Inc. and Celonic Group are collaborating to produce the novel human recombinant protein AT-100 as a therapeutic candidate against COVID-19. Based on the agreement, Celonic will be responsible for process optimization and GMP manufacturing of AT-100 for clinical study. AT-100 is an engineered version of an endogenous protein and has shown potential in addressing the inflammation and injury caused by serious, infection-driven respiratory diseases in preclinical studies but has never been produced for larger-scale clinical trial indications. Airway has previously filed a pre-IND submission with the U.S. Food and Drug Administration for AT-100 as a preventive treatment of the serious respiratory disease bronchopulmonary dysplasia in very preterm infants, with an IND filing expected in Q3 and plans to enter the clinic in late 2020. Celonic expects to begin production of AT-100 in June 2020. Press release.

In the latest milestone for the Mutational Dynamics of SARS-CoV-2 in Austria project, 216 SARS-CoV-2 genome sequences have now been completed and released by CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences, in close collaboration with the Medical University of Vienna, the Medical University of Innsbruck and the Austrian Agency for Health and Food Safety. CeMM researchers have also published a dedicated website offering background information as well as interactive access to the data for scientists and laypeople alike. The virus genomes can be explored interactively and intuitively via advanced visualization tools provided by CeMM and the open source project Nextstrain. The collaborative initiative aims to elucidate 1,000 SARS-CoV-2 genomes in Austrian patients using cutting-edge next-generation sequencing techniques and sophisticated computational analyses. The first 21 genome sequences published on un early April. The latest release indicates the pool of circulating viruses in the early phase of the pandemic was already highly diverse, with some viruses leading to bigger transmission clusters than others. It also provides independent support for many epidemiological findings resulting from contact tracing, as well as evidence for multiple viruses circulating at the same time. The molecular sequence analysis revealed on average 6.9 mutations per viral genome, of which more than four resulted in changed amino acids. Press release.

A COVID-19 vaccine candidate developed by the University of Saskatchewan's (USask) Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) has cleared another major milestone in moving towards human clinical trials. The novel vaccine has proven highly effective in ferrets, with two immunization inducing a strong immune response, generating neutralizing antibodies, and decreasing viral infection in the upper respiratory tract to almost undetectable levels. The vaccine was formulated with a combination adjuvant previously created in partnership with Dalhousie University, the University of British Columbia, and the South Korean-based International Vaccine Institute, with funding from the Bill and Melinda Gates Foundation. Several additional studies are planned over the next few months, with human clinical trials planned for this fall. VIDO-InterVac is also completing a vaccine manufacturing facility that will be GMP-certified to support vaccine production capacity in Canada. Press release.

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