“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.”
The Coronavirus (COVID-19) pandemic has taken the world by storm with over 380K+ cases confirmed worldwide and 16K+ deaths as of this writing.1 Although the word “pandemic” strikes fear into most people, it is simply defined as “a disease prevalent over a whole country or the world.” There have been many pandemics throughout history that have been overcome. Furthermore, it is important to remember that a small percentage of people infected with COVID-19 succumb to the virus (~4%) ― and most successfully recover. (Refer to the infographic below to explore the history of pandemics.)
Scientists are working 24/7 to develop vaccines and treatments as quickly as possible to meet the increasing needs of those affected, and progress is being made at an astonishing pace. Here we summarize some of the key scientific breakthroughs and developments that are underway right now.
The science behind COVID-19 coronavirus infection
Novel corona virus (nCoV) is also known as SARS-CoV-2 and is a single-stranded, RNA-containing virus that infects the host cell by attaching to proteins on the cell surface, e.g., ACE2, using its surface glycoprotein (spike S protein) (see Figure 1). Once inside the host cell, the virus multiplies to generate to new virus particles, i.e., buds, to infect new host cells.
Figure 1: COVID-19 infection process
Source: TargetScape in Integrity, a Cortellis solution
Key scientific breakthroughs and treatments
Recent scientific breakthroughs have paved the way for researchers to identify drug targets and vaccines to treat or prevent the virus:
- Complete genome sequence of SARS-CoV2 isolated from infected patients published2
- Atomic structure of spike protein published, a promising target for a COVID-19 vaccine3
- ACE2 identified as the host cell entry receptor for SARS-CoV-24
Furthermore, rapid progress has been made to clinically test drugs and vaccines in patients, including:
- Chloroquine, an anti-malarial drug that was launched by Sanofi in 1949, is currently being evaluated in multiple clinical trials in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19).
- Remdesivir, a nucleoside RNA polymerase inhibitor against Ebola virus, was developed by Gilead Sciences, Inc. The FDA approved the investigational new drug (IND) filing of Remdesivir for the treatment of COVID-19. This was followed by Gilead’s announcement of two Phase 3 clinical studies of Remdesivir for COVID-19 at the University of Nebraska Medical Center, Omaha, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).
- Favipiravir, an RNA polymerase inhibitor originally developed for the treatment of influenza by Fujifilm Toyama Chemical has been shown to be effective in treating patients with COVID-19 and will be promoted by the Chinese government for treatment of COVID-19.
- mRNA-1273 vaccine against COVID-19 was developed by NIAID researchers in collaboration with Moderna, Inc. A Phase 1 study of mRNA-1273 vaccine has begun at Kaiser Permanente Washington Health Research Institute (KPWHRI), Seattle and is funded by NIAID.
- LV-SMENP-DC vaccine against Spike glycoproteins on SARS-CoV-2 was developed by Shenzhen Geno-Immune Medical Institute and is in early Phase 1/2 clinical trials for the treatment of COVID-19.
- INO-4800 vaccine against COVID-19 was designed by INOVIO Pharmaceuticals, Inc. Preclinical studies were started in early 2020 and clinical trials are expected to commence by April 2020. INOVIO has received grants of $9 million from the Coalition for Epidemic Preparedness Innovations (CEPI) and $5 million from the Bill & Melinda Gates Foundation.
In addition to these clinical developments, Cortellis Drug Discovery Intelligence reports 589 drugs targeting coronavirus proteins (Figure 2), of which 72 are specific for the treatment of COVID-19. Of these 72 drugs, 24 are launched or registered drugs for other indications that are now being investigated for the treatment of COVID-19. Twenty are vaccines for the prevention of COVID-19, of which three are in Phase 1 or Phase 1/2 trials already.
Figure 2: Potential targets for COVID-19 vaccines
An alternative mechanism to identify potential drugs for COVID-19 is to look for similar drugs using a structure similarity search tool, like what is found in Cortellis Drug Discovery Intelligence. This capability provides researchers with the ability to identify drugs with a similar structure to a known entity. For example, 35 drugs were found to have >80% similarity to Remdesivir, some of which may prove to be effective in treating COVID-19.
Figure 3: Structure of Remdesivir
Figure 4: Structures with 80% similarity to Remdesivir
Resources to support scientific and medical research
The rapid progress being made to identify the causes and potential treatments for COVID-19 provides confidence that scientific innovation will ultimately beat this virus.
At Clarivate, we are committed to supporting this research and have established a Coronavirus resource website, which provides free access to Cortellis Drug Discovery Intelligence, a disease briefing on Coronaviruses, clinical trial data, key scientific articles from Web of Science, and articles from BioWorld (400+ published to date). The site also features complementary access to Cortellis Generics Intelligence, which can be used to help identify alternative sources of APIs to continue drug production to minimize drug shortages. The site is continually updated, so be sure to bookmark it and return often. We also have a launched a Chinese language resource site to support research efforts there.
- Andersen, K.G., Rambaut, A., Lipkin, W.I. et al The proximal origin of SARS-CoV-2. Nat Med (2020). https://doi.org/10.1038/s41591-020-0820-9
- Wrapp, D. et al RAPP Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (2020). 1260-1263 https://doi.org/10.1126/science.abb2507
- Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020. https://doi.org/10.1038/s41586-020-2012-7