Immuron reports neutralizing activity against SARS-CoV-2

Date Posted:23 July 2020 

 

Immuron is pleased to announce that IMM-124E, the technology platform used to manufacture the company’s over-the-counter gastrointestinal & digestive health immune supplements Travelan® and Protectyn® has demonstrated neutralizing activity against SARS-CoV-2, the virus that causes COVID-19, in laboratory studies. This finding demonstrates the potential to further investigate IMM-124E as a new oral therapeutic approach to target SARS-CoV02 in the GI tract.

The cytopathic effect inhibition cell-based assay was established and performed by 360 biolabs, a Melbourne based Contract Research Organization using the SARS-CoV-2 hCoV-19/Australia/VIC01/2020 virus obtained from Melbourne’s Peter Doherty Institute for Infection and Immunity. The in-vitro assessment of the neutralization of SARS-CoV-2 was performed on four production lots of product used to manufacture Travelan® and Protectyn®. The In-vitro susceptibility of the virus to IMM-124E was determined using the quantitative assay which measures virus replication in the presence of increasing concentrations of the product compared to replication in the absence of the product. The effective concentration of IMM-124E was reported as the concentration of the product at which virus replication is inhibited by 50 percent (EC50) or 90 percent (EC90).

All four production lots produced mean EC50 values of 40.5 to 91.9 ug/mL and inhibited viral replication at concentrations which there was no observed cell toxicity. The concentration of IMM-124E at which virus replication was inhibited by 90 percent (EC90) produced mean EC90 values ranging from 48.7 to 155.4 ug/mL for all four lots tested again at concentrations at which there was no observed cell toxicity. A commercially available high protein milk powder product was used as a placebo in the studies and produced EC50 values greater than the observed cellular cytotoxicity concentration of >4800 ug/mL. The control milk powder inhibited viral replication at doses >25,000 ug/mL and more importantly did not inhibit viral replication at doses which it was cytotoxic to cells.

Another major finding made during the study was that cell viability in the presence of IMM-124E was greatly enhanced when compared to placebo. IMM-124E improved cell viability by 180 to 260% relative to controls. These results indicate that IMM-124E at concentrations which inhibited SARS-CoV-2 replication improved cell viability.

Bovine coronavirus is widely prevalent in dairy cows and is transmitted by infected feces being taken in via the mouth or nose. The virus initially infects cells in the small intestine, and then spreads through to the colon. The major source of coronavirus is adult cattle carriers shedding the virus in their feces and thereby exposing the newborn calves.

Bovine coronaviruses (BCoVs) cause respiratory and enteric infections in cattle including;

• severe diarrhea in newborn calves

• winter dysentery in adult cows

• bovine infectious respiratory disease (BIRD) in calves and adult cattle

Prophylaxis of BCoV enteric disease in newborn calves is usually obtained by means of vaccination of pregnant cows to enhance the level of maternal antibodies that are transferred to their offspring through colostrum, thus exerting a local protective effect against BCoV-induced enteritis. Specific treatment and prevention of coronavirus also involves the feeding of antibodies against coronavirus. This can be achieved by feeding the antibody rich colostrum from coronavirus vaccinated animals, to calves for the first few weeks of life. Therefore, the possibility of producing a Hyper-immune Bovine Colostrum to severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is quite high. However, the prevalence and prognosis of digestive system involvement and gastrointestinal symptoms in patients with COVID-19 remains largely unknown.

Colostrum is a complex biological fluid that is rich in nutritional components (vitamins, minerals, and amino acids), immune regulating compounds (immunoglobulins, lactoferrin, cytokines and antimicrobial peptides) and growth factors. The main functions of colostrum are to provide essential nutrients, strengthen the natural defense system, modulate immune response, balance intestinal microbiota, promote tissue growth and maturation of the digestive tract in newborns. Colostrum also has antiviral, antifungal and antibacterial properties which enable it to kill different pathogens like Escherichia coli, rotavirus and Cryptosporidium.

Bovine coronaviruses belong to the family Coronaviridae in the order Nidovirales and are members of subgroup 2a along with swine hemagglutinating encephalomyelitis virus (HEV), canine respiratory CoV, and human CoV-OC43 and HKU1. HEV, which causes wasting disease, is an exception; the others all cause enteric and/or respiratory disease. The severe acute respiratory syndrome (SARS)-CoVs, which are associated with respiratory and enteric infections in humans and animals (eg, civet cats, raccoon dogs, bats), belong to the CoV subgroup 2b.1.

“Armed with the knowledge of Bovine coronavirus enteric disease we were interested in testing IMM-124E against SARS-CoV-2” said Dr Jerry Kanellos, CEO of Immuron Limited.

“We know that SARS-CoV-2 causes an influenza-like disease that is primarily thought to infect the lungs with transmission through the respiratory route ranging from mild respiratory symptoms to severe lung injury, multiorgan failure, and death. Respiratory symptoms have dominated the clinical focus, however gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain are also observed in a growing subset of patients often presenting with no respiratory symptoms. In the United States the Centers for Disease Control and Prevention recently updated the symptoms of coronavirus to include diarrhea. This growing clinical evidence suggests that the Gastrointestinal tract may present another viral target organ. The virus RNA has been detected in anal swabs of patients even after nasopharyngeal testing has turned negative, and cells in the inner-gut lining express high amounts of the angiotensin-converting enzyme 2 (ACE2) receptor that SARS-CoV-2 uses to gain entry to cells implying the potential for gastrointestinal infection and a fecal–oral transmission route. If fecal–oral transmission is a significant factor in the pandemic then the consequences for an oral therapeutic would be significant, however the research is still inconclusive. The preliminary data set we have generated potentially offers a new oral therapeutic approach to target and directly inhibit the virus in the Gastrointestinal tract and warrants further evaluation to identify the inhibitory substances in our products. The company has filed a provisional patent application in respect of the findings.”