Coronaviruses are a large family of viruses that cause illnesses like the common cold, but can also cause more severe diseases such as Middle East Respiratory Syndrome (MERS) and Sever Acute Respiratory Syndrome (SARS). The novel coronavirus SARS-CoV-2 was identified in 2019 in Wuhan, China, and has now spread around the world with currently over 17 million cases (reference) . Whilst symptoms are generally mild and most patients make a full recovery, the infection can be more serious, and potentially fatal, for older patients and those with underlying health issues.
Whilst various treatment options are in development for SARS-CoV-2, testing has initially been the focus of the global response to the pandemic, including antigen testing to identify infected individuals, and antibody testing for those who have previously been infected and are now potentially immune. The development of a vaccine is also an essential step in the long-term control of the COVID-19 disease, with many programmes ongoing around the world, however it is estimated that it could take at least a year before a vaccine against COVID-19 is approved. In parallel, ’neutralising’ therapies have been identified that could prevent the virus from infecting human cells, and therefore offer the potential for more immediate effect in patients (reference).
Neutralising therapies harness the ‘blocking’ ability of neutralising monoclonal antibodies, synthesised in the laboratory to mimic natural antibodies. These antibodies can inhibit the infectivity of a pathogen by interfering with attachment to cells, or preventing viral particles from undergoing structural changes required for cell entry. This treatment has the potential to be given as a preventative option for those more at risk of being exposed to the virus (such as health and social care workers) to provide protection, as well as to patients already infected by the virus to help treat and prevent disease progression. This treatment option has been explored for similar coronaviruses, such as SARS, and has been found to reduce disease severity and viral burden in animal models (reference).
The SARS-CoV-2 coronavirus is ~1/10,000 of a millimetre in size and consists of four structural proteins: the spike, envelope, membrane and nucleocapsid. The virus has three main actions necessary for successful host infection: to deliver genetic instructions in the form of viral RNA across the membrane of uninfected cells, to allow newly-synthesised RNA to escape from an infected cell, and to protect the RNA during its journey to discover new, uninfected cells (reference). The spike protein is used as the mechanism of cell entry, by binding to specific angiotensin converting enzyme 2 (ACE2) receptors on the surface of a human cell. Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain (reference). Blocking this interaction between the spike protein and ACE2 therefore offers a potential method to stop the infection process in humans.
The infection process
Avacta is able to engineer its Affimer proteins with a binding area that can be varied very precisely to bind new targets, such as the spike protein of SARS-CoV-2. Compared with antibodies, these proteins have key benefits as virus neutralising therapies. Their small size and high solubility means that a much higher concentration of Affimer molecules can be used in the drug formulation, to more effectively block the spike proteins on each virus particle and better protect the patient from infection. Additionally, bispecific and trispecific Affimer neutralising therapies that bind to more than one part of the spike protein could ensure the effectiveness of the neutralising therapy even if the virus’ spike protein mutates.
Avacta was able to generate Affimer binders to the SARS-CoV-2 virus within just four weeks of receiving the viral protein, and on 18 June 2020 we announced that collaborative work with the Centre for Virus Research at the University of Glasgow had shown these Affimer proteins prevent infection of human cells by a SARS-CoV-2 model virus, and therefore provide a potential therapy for COVID-19 infection. Work is continuing to further study the way in which the proteins prevent infection and on 29th July we announced an expansion of our partnership with Daewoong Pharmaceutical to to develop stem cell therapies for COVID-19 and future pandemic diseases.