The mysterious coronavirus outbreak in the Chinese city Wuhan now termed as Covid-19, and its fast spread to many other countries, endangers thousands of lives. The pandemic has catalysed the development of novel coronavirus vaccines across the biotech industry, both by pharmaceutical companies and research organisations such as the National Institutes of Health (NIH), US.
The first Covid-19 vaccine in China is expected to be ready for clinical trials by the end of April, according to Xu Nanping, China’s vice-minister of science and technology.
Health officials from WHO have noted that Gilead’s remdesivir has demonstrated efficacy in treating the coronavirus infection. The US commenced clinical trials in humans at the University of Nebraska Medical Center to test the safety and efficacy of the drug. The first patient to be administered the drug is an evacuee from the Diamond Princess cruise ship.
Favilavir, the first approved coronavirus drug in China
The National Medical Products Administration of China has approved the use of Favilavir, an anti-viral drug, as a treatment for coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial involving 70 patients. The clinical trial is being conducted in Shenzhen, Guangdong province.
Pharmaceutical companies involved in developing coronavirus drugs/vaccines
Here is a list of the major coronavirus drugs that pharmaceutical companies across the world are developing that have the potential to become major coronavirus vaccines or antivirals for treating the contagious coronavirus infection.
Novel coronavirus vaccines
TNX-1800 by Tonix Pharmaceuticals
Tonix Pharmaceuticals has partnered with Southern Research, a non-profit research organisation, to develop a coronavirus vaccine named TNX-1800. The vaccine is a modified horsepox virus developed using Tonix’s proprietary horsepox vaccine platform.
TNX-1800 is designed to express a protein derived from the virus that causes the coronavirus infection. Southern Research will be responsible for evaluating the efficacy of the vaccine, under the partnership.
Brilacidin by Innovation Pharmaceuticals
Innovation Pharmaceuticals announced that it is evaluating Brilacidin, a defensin mimetic drug candidate, as a potential treatment for coronavirus. Brilacidin has shown antibacterial, anti-inflammatory and immunomodulatory properties in several clinical trials.
The company is planning to explore research collaborations and seek federal grants to develop the coronavirus drug. It is already investigating the drug for inflammatory bowel disease and oral mucositis in cancer patients.
INO-4800 by Inovio Pharmaceuticals and Beijing Advaccine Biotechnology
Inovio Pharmaceuticals has collaborated with Beijing Advaccine Biotechnology Company to advance the development of the former’s vaccine, INO-4800, as a novel coronavirus vaccine. The company has started pre-clinical testing for clinical product manufacturing.
The vaccine development is supported by a $9m grant from the Coalition for Epidemic Preparedness Innovations (CEPI).
Inovio aims to progress the vaccine through phase one human testing in the US to test safety and efficacy. A phase one clinical trial is planned to be conducted in parallel in China, by Beijing Advaccine.
Recombinant subunit vaccine by Clover Biopharmaceuticals
Clover Biopharmaceuticals is developing a recombinant subunit vaccine using its patented Trimer-Tag© technology. The company is developing the vaccine based on the trimeric S protein (S-Trimer) of the 2019-nCoV virus, which is responsible for binding with the host cell and causing a viral infection.
Using Trimer-Tag© technology, Clover successfully produced the subunit vaccine in a mammalian cell-culture based expression system on 10 February. The company also identified antigen-specific antibody in the serum of fully recovered patients who were previously infected by the virus.
A highly purified form of the S-Trimer vaccine is expected to be available in six to eight weeks for performing pre-clinical studies. The company is equipped with in-house cGMP biomanufacturing capabilities to scale-up production if the vaccine is proven to be successful.
Clover is also collaborating with GSK to develop a vaccine using the latter’s pandemic adjuvant system.
Vaxart’s coronavirus vaccine
Vaxart is developing an oral recombinant vaccine in tablet formulation using its proprietary oral vaccine platform, VAAST.
The company plans to develop vaccines based on the published genome of 2019-nCOV to be tested in pre-clinical models for mucosal and systemic immune responses.
CytoDyn is examining leronlimab (PRO 140), a CCR5 antagonist, as a potential coronavirus drug.
The drug is already being investigated in phase two clinical trials as a treatment for HIV and has been awarded fast-track approval status by the United States Food and Drug Administration.
Linear DNA Vaccine by Applied DNA Sciences and Takis Biotech
Applied DNA Sciences’ subsidiary LineaRx and Takis Biotech formed a joint venture on 07 February to develop a linear DNA vaccine as a treatment for coronavirus. The JV will use Polymerase Chain Reaction (PCR)-based DNA manufacturing technology to develop the vaccine.
The PCR technology offers several advantages including high purity, increased production speed, and absence of antibiotics and bacterial contaminants. Further, the vaccine gene developed through this technology can be effective without being inserted into the patient’s genome.
BXT-25 by BIOXYTRAN to treat late-stage acute respiratory distress syndrome (ARDS)
BIOXYTRAN announced that it is exploring partners to develop its lead drug candidate, BX-25, as a treatment for Acute Respiratory Distress Syndrome (ARDS) in late-stage patients infected with the coronavirus. The diffusion of oxygen to the blood is comprised in patients suffering from ARDS leading to fluid build-up in the lungs.
BX-25 is designed to be 5,000 times smaller than blood cells and efficiently transport oxygen through the body for a period of nine hours before being processed by the liver. The drug can help in supplying oxygen to the vital organs and enable the patient to recover and survive.
MERS CoV vaccines for coronavirus
Novavax’s MERS coronavirus vaccine candidate
Novavax developed a novel Middle East Respiratory Syndrome (MERS) coronavirus vaccine candidate in 2013, post the identification of the first MERS coronavirus ((MERS-CoV) in Saudi Arabia in 2012. It is a crucial target for coronavirus vaccine development by the Coalition for Epidemic Preparedness Innovations (CEPI) and is a priority disease for the World Health Organisation (WHO).
The candidate is designed to primarily bind to the major surface S-protein and developed using the company’s recombinant nanoparticle vaccine technology. Tested along with the Novavax’s proprietary adjuvant Matrix-M™, it inhibited infection by inducing immune responses in the laboratory studies.
Novavax has produced several nanoparticle vaccine candidates for testing in animal models. The company aims to carry out human trials in 2020.
The MERS coronavirus is related to the severe acute respiratory syndrome (SARS) coronavirus for which the company had previously developed a recombinant nanoparticle vaccine candidate.
Inovio Pharma’s INO-4700
The investigational DNA immunotherapy, INO-4700 (GLS-5300) is being developed by Inovio in partnership with GeneOne Life Science. It is delivered as vaccine intramuscularly, using the Cellectra® delivery device.
The vaccine was well-tolerated and demonstrated high immune responses against the MERS-CoV in 94% of patients in the early-stage clinical trial in July 2019.
It also generated broad-based T cell responses in 88% of the subjects.
“Research organisations such as the National Institutes of Health (NIH), US are also developing a vaccine for the coronavirus.”
Remdesivir (GS-5734) by Gilead Sciences
An ebola drug developed by Gilead Sciences that was found to be ineffective is now being tested in phase III randomised clinical trial in partnership with China.
The trials are being performed on 761 patients in a randomised, placebo-controlled, double-blind study at multiple hospitals in Wuhan, the epicentre of the novel coronavirus outbreak. The results from the trials are expected to be available over the next few weeks.
According to a report by The New England Journal of Medicine (NEJM), remdesivir, when administered to a coronavirus patient in the US, appeared to have improved the clinical condition.
Biocryst Pharma’s Galidesivir, a potential antiviral for coronavirus treatment
The antiviral drug Galidesivir (BCX4430) has shown broad-spectrum activity against a wide range of pathogens including coronavirus. It is a nucleoside RNA polymerase inhibitor that disrupts the process of viral replication.
The drug has already shown survival benefits in patients against deadly viruses such as Ebola, Zika, Marburg, and Yellow fever.
Galidesivir is currently in advanced development stage under the Animal Rule to combat multiple potential viral threats including coronaviruses, flaviviruses filoviruses, paramyxoviruses, togaviruses, bunyaviruses, and arenaviruses.
Discovered by Regeneron, the combination of neutralising monoclonal antibodies REGN3048 and REGN3051 is being studied against coronavirus infection in a first-in-human clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The safety and tolerability of the drug will be studied in 48 patients.
Both the antibodies bind to S-protein of MERS coronavirus. The intravenous administration of the drug in the mouse model of MERS resulted in the high-level neutralisation of the MERS coronavirus in circulating blood with reduced viral loads in the lungs.
Other companies developing coronavirus vaccines/drugs
Companies such as Inovio Pharmaceuticals, Moderna, and Novavax have been reported to be developing coronavirus vaccines. A total of 30 therapies are planned to be tested, including few traditional medicines for coronavirus treatment by Chinese scientists. Chloroquine phosphate has shown efficacy in treating symptoms of the disease, among the 30 therapies. Patients administered with the drug achieved a better drop in fever and shorter recovery time in clinical trials being conducted in hospitals in the Guangdong province and Hunan province.
Vaccine by Generex
Generex has announced that it is developing a COVID-19 vaccine following a contract from a Chinese consortium comprising of China Technology Exchange, Beijing Zhonghua Investment Fund Management, Biology Institute of Shandong Academy of Sciences and Sinotek-Advocates International Industry Development.
The company will utilise its Ii-Key immune system activation technology to produce a Covid-19 peptide for human clinical trials.
Generex will receive an upfront payment of $1m to commence the groundwork for the vaccine development and $5m licensing fee for its Ii-Key technology. It is also eligible to receive a 20% royalty on every dose of vaccine produced under the contract.
Coronavirus drugs by Columbia University
Researchers at Columbia University have been awarded a $2.1m grant by the Jack Ma Foundation to develop a coronavirus cure. Four different teams at the university will adopt various approaches towards the development of a vaccine against coronavirus.
Vaccine by Tulane University
Tulane University has launched a research programme to identify a potential medicine for coronavirus in the form of a vaccine. The university will utilise a grant from the Brown Foundation to carry out the research activities.
Coronavirus vaccine by ImmunoPrecise Antibodies
ImmunoPrecise Antibodies has launched a vaccine and therapeutic antibody programme to develop a vaccine as well as antibodies against Covid-19. The company will use its B Cell Select™ and DeepDisplay™ discovery platforms to therapeutic compounds against the coronavirus.
Serum Institute of India
Serum Institute of India (SII) is collaborating with Codagenix, a US-based biopharmaceutical company, to develop a coronavirus cure using a vaccine strain similar to the original virus. The vaccine is currently in the pre-clinical testing phase, while human trials are expected to commence in the next six months. SII is expected to launch the vaccine in the market by early 2022.
Zydus Cadila announced the launch of an accelerated research programme to develop a vaccine for Covid-19 using two novel approaches. The first approach includes the development of a DNA vaccine against the viral membrane protein of the virus, while a live attenuated recombinant measles virus (rMV) vectored vaccine will be developed in the second approach. The rMV-based vaccine works by inducing specific neutralising antibodies, which will provide protection from the coronavirus infection.
NanoViricides, a clinical-stage company, is working on developing a treatment for nCoV-2019 using its nanoviricide® technology. The company’s technology is used to develop ligands that can bind to the virus in the same way as a cognate receptor and attack various points of the virus.
Vir Biotechnology, a clinical-stage immunology company, announced on 12 February that it has identified two monoclonal antibodies that can bind to the virus that causes Covid-19. The antibodies target the spike (S) protein of the virus by entering through the cellular receptor ACE2.
The company has formed a partnership with WuXi Biologics on 25 February to commercialise the antibodies identified to treat coronavirus. If approved, Wuxi will have the rights to market the therapies in China, while Vir will retain the marketing rights in other countries.
HIV drugs for coronavirus treatment
An HIV protease inhibitor, lopinavir is being studied along with ritonavir for the treatment of MERS and SARS coronaviruses. The repurposed drug is already approved for the treatment of HIV infection under the trade name Kaletra®.
The combination is listed in the WHO list of essential medicines. Lopinavir is believed to act on the intracellular processes of coronavirus replication and demonstrated reduced mortality in the non-human primates (NHP) model of the MERS.
Lopinavir/ritonavir in combination with ribavirin showed reduced fatality rate and milder disease course during an open clinical trial in patients in the 2003 SARS outbreak.
Cipla is also reportedly planning to repurpose its HIV drug LOPIMUNE, which is a combination of protease inhibitors Lopinavir and Ritonavir, for the treatment of coronavirus.
A licensed generic of Kaletra®, LOPIMUNE is currently available in packs of 60 tablets each, containing 200mg of Lopinavir and 50mg of Ritonavir.
Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson, donated its PREZCOBIX® HIV medication (darunavir/cobicistat) for use in research activities aimed at finding a treatment for Covid-19.
Darunavir is a protease inhibitor marketed by Janssen. Anecdotal reports suggest darunavir as potentially having antiviral activity against Covid-19. It is, however, currently approved only for use with a boosting agent, and in combination with other antiretrovirals, for the treatment of HIV-1.
Janssen has no in vitro or clinical data to support the use of darunavir as a treatment for Covid-19. The drug is in the process of being evaluated in vitro for any potential activity against the coronavirus.
Further, Janssen has partnered with the Biomedical Advanced Research and Development Authority (BARDA) to expedite the development of a Covid-19 treatment.
The Coronavirus outbreak
The contagious coronavirus outbreak at the end of 2019, which the WHO named as Covid-19, led to a medical emergency across the world.
Similar infections are caused by human alpha and beta coronaviruses such as 229E, NL63, OC43 and HKU1.
What are the symptoms?
Coronavirus symptoms include those associated with common cold, such as running nose, headache, cough, fever, and sore throat.
“Coronavirus transmission can happen human-to-human as well as from infected animals such as dogs and cats.“
Covid-19 is a betacoronavirus that has origin in bats, according to the Centers for Disease Control and Prevention (CDC).
Believed to have transmitted from animals and reptiles such as snakes, coronaviruses cause respiratory issues such as upper respiratory tract illnesses and lower respiratory illnesses such as pneumonia and bronchitis.
Coronavirus transmission can happen human-to-human as well as from infected animals such as dogs and cats.