Towards the end of December 2019, Chinese authorities reported to the World Health Organization (WHO) about the severe pneumonia-like cases1. Soon after it, the virus started spreading its reach in other parts of the world like Europe, other Asian countries and the US. With the prolific enhancement in death toll across China within one month, WHO declared the epidemic as a public health emergency of international concern. The epidemic has created huge unrest among the public, health officials, R&D companies, research institutes, and various other government agencies all over the world. Unfortunately to date, no drug or vaccine has yet been approved to cure human coronaviruses. Very recently, in the US, Gileads nucleoside analogue remdesivir (an experimental drug) has been launched into a phase III trial for the treatment of the novel coronavirus.
Key Figures and Countries Under Impact:
| 94,200 total infected cases.
3,219 total deaths.
2,981 deaths in Hubei Mainland China.
50,690 total recovered cases.
80+ countries have confirmed cases of coronavirus.
| No. of Countries With Reported Cases In Different Region
China has 80,282 infected cases followed by South Korea 5,621. There are 33 European countries which have report COVD-19 infection among which, Italy is the most affected and have 2,502 infected cases.
Biology of Coronavirus
The coronavirus epidemic is caused by the novel beta-coronavirus, named 2019-nCoV or COVID-19 (now named as SARS-CoV-2). It shows significant genetic homology with SARS-CoV and other bat coronaviruses4. The 2019-nCoV genome, close to SARS and MERS, encodes non-structural proteins such as 3-chymotrypsin-like protease, papain-like protease, helicase, and RNA-dependent RNA polymerase, structural proteins like spike glycoprotein and accessory proteins. Notably, these four non-structural proteins play a pivotal role in the life cycle of the virus along with the spike glycoprotein which is essential for receptor-mediated entry into the host cells. After entering the host, the virus manipulates the anti-inflammatory pathways in its favor and evades the host immune response. Therefore, the above-mentioned proteins have allured the research community as a potential target for developing therapeutic molecules.
Potential Therapeutic Approaches
Since 2019-nCoV shows significant genomic and proteomic homology with the various conserved region with previous SARS and MERS strains, previously explored therapeutic approaches which target common drug-binding pockets in the conserved vital enzymes is definitely one of the options which are on priority.
Agents Targeting Vital Viral Biomolecules
There are various susceptible targets in viruses among which, nucleic acid and protein or enzyme of virus can act as a prime target. For nucleic acid, nucleoside analogues are popularly used and have also shown promising potentials as in previous MERS and SARS cases. These nucleic acid Nucleoside analogs abrogate viral RNA synthesis by targeting the RNA-dependent RNA polymerase. The protease inhibitors target viral enzymes by blocking the active sites.There are also a couple of existing protease inhibitors that can be explored in the current scenario. Some of these potential drugs or inhibitors have been mentioned below:
- Favipiravir and Ribavirin, which are an approved nucleoside analogues
- Remdesivir and Galidesivir, which are an experimental nucleoside analogues
- Disulfiram, Lopinavir and Ritonavir, which are approved protease inhibitors
Agents Targeting Host Biomolecules
Delivery of host agents in order to boost effective anti-viral immunity can be one of the strategies. However, it has its own consequences like hyper-immune side effects that need to be addressed. Some of the potential strategies have been highlighted below:
- Delivering pro-inflammatory cytokines to host. The cytokine may be modified in order to enhance its stability like pegylation, sialylation, etc.
- Inhibitors of receptors in the host for viral entry
- Therapeutic nucleic acid-based strategies
However, it is important to note the targeting host agents in antiviral therapy has not been very encouraging in the past. Combination therapy of agents targeting viruses and host can be also explored.
Key Hurdles for Drug Development
- Pre-production and upstream processing of viral isolates/strains for drug R&D is not easy and risk-free. In addition, the reverse genetics-based approach needs heavy standardization.
- Manufacturing or production of virus particles in a mammalian cell line is complicated and requires a high level of monitoring and safety.
- Post-production issues like testing in animal models followed by humans, lengthy drug approval processes and the lack of clinical trial candidates for trying potential approved or experimental drugs.
Key Industrial Players in the Hunt
|Collaborating with the Chinese health authorities to develop clinical trials to assess an experimental remdesivir|
|Signed an agreement with United States. Health and Human Services Department (HHS) to develop new drugs to combat novel coronavirus|
|RNA based firm have planned to work on the therapeutic approaches to treat coronavirus|
|Have partnered with the University of Queensland’s COVID-19 vaccine development program on adjuvant technology, MF59®|
|Have partnered with U.S. Department of Health & Human Services (HHS) to identify therapeutic candidates with antiviral activity|
|Have planned to work on U.S. Department of Health & Human Services (HHS) to identify therapeutic candidates with antiviral activity|
|Have planed to partner with Chinese biotech company Clover Biopharmaceuticals in order to provided its proprietary adjuvants – compounds for increasing the effectiveness of vaccines|
|Working on animal models with its recombinant protein nanoparticle technology platform to produce antigens obtained from the coronavirus spike (S) protein.|
|Working on DNA vaccines (INO-4800) against COVID-19.|
|With Imperial College London, they are trying to explore the existing databases in order to find potential drugs|
|Has recently announced AI algorithms based on six new molecules that can target viral replication in the host|
Coronavirus was first discovered in the 1960s in avian species. After that, series of new viral strains were discovered and given various names like SARS-CoV in 2003, HCoV NL63 in 2004, HKU1 in 2005, MERS-CoV in 2012, and 2019-nCoV (now named as SARS-CoV2) in 2019. The quick patent landscape overview has been presented below:
Patent Priority Trend
Note: The above analysis has been done in a quick manner on our XLPAT tool. In addition, the analysis includes other previously known strains of coronavirus as well.
There are some granted patents related to other strains of Coronavirus which are different from the recent SARS-CoV-2.
|EP3172319B1||Pirbright Institute||The patent protects an attenuated coronavirus comprising a variant of the replicase gene, obtained from the avian infectious bronchitis virus, that belong to Gammacoronavirus genus|
|EP2898067B1||Dr. Soliman Abdulkhader Fakeeh Hospital Company | Erasmus University Medical Center Rotterdam||The patent protects the MERS-CoV virus, as well as in vitro methods for diagnosing infections caused by this virus and the use of the MERS-CoV virus|
|US7220852B1||Department of Health And Human Services||This patent actually protects the nucleic acid sequence of the SARS-CoV virus, and was granted in 2007. However, the patent is no longer active now.|
Key Future Possible Impacts :
- The coronavirus outbreak has stimulated significant financial crisis all over the world with China in the epicentre. The Organization for Economic Cooperation and Development (OECD) has warned that the global economy will grow at the slowest rate since the year 2009.
- Existing approved and experimental drugs against previous viral outbreaks such as Ebola, SARS or MERS will be under the priority of health agencies for developing an immediate cure.
- Various countries, more specifically China, will rely on compulsory licensing procedures to manufacture or use patent drugs against coronavirus.
- RnD for broad-spectrum antiviral therapy will be the focus of future anti-viral therapy programs as compared to the approaches for treating specific cases.
- Inter and Intra governments and industrial agencies collaboration will increase worldwide in order to smoothen the process of fighting against COVD-19
- In order to fasten the drug discovery process, AI-based approaches will be heavily exploited using viral genomic, proteomic and drug databases. The AI/Machine learning-based approaches may be used to know more about virus structure, potential drug binding sites, inhibitors or drug, their screening, and diagnostic procedures.
- Morse, J. S., Lalonde, T., Shiqing, X. & Liu, W. R. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019‐nCoV. ChemBioChem https://doi.org/10.1002/cbic.202000047 (2020)
- Zumla, A., Chan, J. F., Azhar, E. I., Hui, D. S. & Yuen, K. Y. Coronaviruses — drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15, 327–347 (2016).
- De Clercq, E. New nucleoside analogues for the treatment of hemorrhagic fever virus infections. Chem. Asian J. 14, 3962–3968 (2019).
- Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. https://doi.org/10.1038/s41422-020-0282-0 (2020).
- De Clercq, E. & Li, G. Approved antiviral drugs over the past 50 years. Clin. Microbiol. Rev. 29, 695–747 (2016)