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.
Caused by human alpha and beta coronaviruses such as 229E, NL63, OC43 and HKU1, the infection is responsible for SARS and MERS.
The mysterious Corinavirus 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 vaccines across the biotech industry, both by pharmaceutical companies and research organisations such as the National Institutes of Health (NIH), US.
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, by Chinese scientists.
Meanwhile, clinical-stage biotech company GeoVax signed a letter of intent with BravoVax, a vaccine developer based in Wuhan, China, to jointly develop a coronavirus vaccine using genetic sequences of the 2019-nCoV.
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.
Here is a list of the major pipeline 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
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 potential treatment for 2019-nCOV. 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.
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-leronlimab
CytoDyn is examining leronlimab (PRO 140), a CCR5 antagonist, as a potential treatment for 2019-nCOV.
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 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
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 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.
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.”
Coronavirus medicines: Drugs being developed for the novel 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.
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.
Regeneron’s REGN3048-3051
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.
Can HIV drugs treat coronavirus infection?
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.
Janssen is also working on developing a vaccine candidate in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), which is part of the Office of the Assistant Secretary for Preparedness and Response (ASPR). It is using its AdVac® and PER.C6® technologies. The technology was previously used to develop an investigational Ebola vaccine.
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