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Home / Analysis / Alternative medical tools against Covid-19

Alternative medical tools against Covid-19

The Covid-19 era has witnessed unprecedented scientific collaboration. Several welcome possibilities have emerged and these have the potential to protect the highest-risk health care workers, while also lessening the severity of Covid-19 in hospitalised patients until the vaccine becomes available.

analysis Updated: Oct 07, 2020, 08:12 IST
Dr Narinder Kumar Mehra
Dr Narinder Kumar Mehra
A health worker collects a swab sample from a passenger to test for Covid-19 infection, Nizamuddin Railway Station, New Delhi, October 5, 2020.
A health worker collects a swab sample from a passenger to test for Covid-19 infection, Nizamuddin Railway Station, New Delhi, October 5, 2020.(Raj K Raj/HT PHOTO)

In the absence of a proven vaccine against Sars-CoV-2, exploring alternative ways to combat the disease is key. The development of targeted reactivated antibodies, discovering new antiviral molecules and other effective tools of immunotherapy could provide a boost to immunity against the virus.

“Designer antibodies”, with neutralising ability for the virus, have become an important tool in treating infectious diseases. The best example is that of a lethal infectious disease caused by the Ebola virus. Researchers developed a therapeutic antibody cocktail involving two fundamentally different antibodies, one from a genetically-humanised mouse and the other from a human survivor with the same disease. Humanised mice are commonly used as small animal models in biomedical research. Their immune system is modified such that it becomes an efficient source of naturally-selected fully human antibodies.

In a recent paper published in Science, scientists at Regeneron Pharmaceuticals Inc. exploited the same technology to successfully generate pairs of highly potent antibodies against the coronavirus spike protein, which could be used as a therapeutic antibody cocktail aimed at minimising the viral load in patients with Covid-19. But why does one need a cocktail of two antibodies? It turns out that individual antibodies, no matter how good, are not potent enough against a devastating disease such as Covid-19 since the virus is able to find ways to escape being neutralised. Regeneron, on September 29, announced the first data of their phase 1/2/3 clinical trial of an investigational antibody cocktail, REGN-COV2. The trial involving 275 patients showed reduced viral load and improved symptoms in non-hospitalised patients. The greatest improvement was observed those who had failed to mount their own effective immune response prior to treatment, suggesting that such a “designer antibody” could emerge as a substitute for the naturally occurring immune response.

No unexpected side-ffects have so far been recorded. The results of the trial have generated so much of confidence that physicians have opted to treat United States (US) President Donald Trump with this “experimental antibody”, with a large dose of eight grams, as against the usual dose of 2.4g.

The second weapon for controlling the spread of the coronavirus is based on a better understanding of the mechanism driving its high infectivity. In a paper published in Science, a team of researchers at the University of Bristol unexpectedly found molecules of a free fatty acid, namely linoleic acid (LA), buried in a tailor-made pocket within the receptor-binding domain of the virus protein. Using the powerful imaging technique, electron cryo-microscopy (Cryo-EM), they were able to decipher the structure of the virus Protein LA complex at a near-atomic resolution. LA is a constituent of linseed oil, used in many industrial processes including the manufacture of linoleum. It is indispensable for many cellular functions including maintenance of cell membranes in the lungs so that we can breathe properly. It plays a vital role in inflammation and immune modulation and is the most likely molecule to which the Sars-CoV-2 attaches itself in order to enter the human body. The next step is to develop a drug that could distort the virus spike protein and prevent it from attaching to the molecules of LA.

The third strategy is based on interferons (IFNs), that get released by host cells in response to the presence of several viruses. Besides their antiviral properties, these molecules play an important role in anti-tumour and immunomodulatory responses. Of the various varieties, type 1 IFN-a is known to influence the development of innate and adaptive immune responses against viral infections.

In a study published in Science, Paul Bastard and colleagues have reported that in about 10% of patients with serious Covid-19, the interferon response gets crippled by the development of neutralising IgG auto-antibodies that attack IFNs itself at the onset of critical disease.

Interestingly, none of the 663 people in a control group with mild or asymptomatic Sars-CoV-2 infection had these rogue antibodies. An interesting feature of this study is that the majority of patients with IFN-attacking antibodies are males (94%) with half of the gravely ill being over 65 years of age. This helps explain why older men face a higher risk of severe disease.

The study raises an important possibility. Could synthetic IFNs given before or soon after the infection help block the virus before it causes severe disease? Interferon therapy has already been approved as immune-boosters in several diseases, including cancer and hepatitis. Several trials have already been initiated for Covid-19 at a dozen universities in the US and Europe and their results point to IFN safety and faster clearance of the virus, particularly if the therapy is initiated early.

The Covid-19-era has witnessed unprecedented swiftness in scientific collaboration. Several welcome possibilities have emerged and these have the potential to protect the high-risk health care workers, while also lessening the severity of Covid-19 in hospitalised patients until the vaccine becomes available.

In the absence of a proven vaccine against Sars-CoV-2, exploring alternative ways to combat the disease is key. The development of targeted reactivated antibodies, discovering new antiviral molecules and other effective tools of immunotherapy could provide a boost to immunity against the virus.

“Designer antibodies”, with neutralising ability for the virus, have become an important tool in treating infectious diseases. The best example is that of a lethal infectious disease caused by the Ebola virus. Researchers developed a therapeutic antibody cocktail involving two fundamentally different antibodies, one from a genetically-humanised mouse and the other from a human survivor with the same disease. Humanised mice are commonly used as small animal models in biomedical research. Their immune system is modified such that it becomes an efficient source of naturally-selected fully human antibodies.

In a recent paper published in Science, scientists at Regeneron Pharmaceuticals Inc. exploited the same technology to successfully generate pairs of highly potent antibodies against the coronavirus spike protein, which could be used as a therapeutic antibody cocktail aimed at minimising the viral load in patients with Covid-19. But why does one need a cocktail of two antibodies? It turns out that individual antibodies, no matter how good, are not potent enough against a devastating disease such as Covid-19 since the virus is able to find ways to escape being neutralised. Regeneron, on September 29, announced the first data of their phase 1/2/3 clinical trial of an investigational antibody cocktail, REGN-COV2. The trial involving 275 patients showed reduced viral load and improved symptoms in non-hospitalised patients. The greatest improvement was observed those who had failed to mount their own effective immune response prior to treatment, suggesting that such a “designer antibody” could emerge as a substitute for the naturally occurring immune response.

No unexpected side-ffects have so far been recorded. The results of the trial have generated so much of confidence that physicians have opted to treat United States (US) President Donald Trump with this “experimental antibody”, with a large dose of eight grams, as against the usual dose of 2.4g.

The second weapon for controlling the spread of the coronavirus is based on a better understanding of the mechanism driving its high infectivity. In a paper published in Science, a team of researchers at the University of Bristol unexpectedly found molecules of a free fatty acid, namely linoleic acid (LA), buried in a tailor-made pocket within the receptor-binding domain of the virus protein. Using the powerful imaging technique, electron cryo-microscopy (Cryo-EM), they were able to decipher the structure of the virus Protein LA complex at a near-atomic resolution. LA is a constituent of linseed oil, used in many industrial processes including the manufacture of linoleum. It is indispensable for many cellular functions including maintenance of cell membranes in the lungs so that we can breathe properly. It plays a vital role in inflammation and immune modulation and is the most likely molecule to which the Sars-CoV-2 attaches itself in order to enter the human body. The next step is to develop a drug that could distort the virus spike protein and prevent it from attaching to the molecules of LA.

The third strategy is based on interferons (IFNs), that get released by host cells in response to the presence of several viruses. Besides their antiviral properties, these molecules play an important role in anti-tumour and immunomodulatory responses. Of the various varieties, type 1 IFN-a is known to influence the development of innate and adaptive immune responses against viral infections.

In a study published in Science, Paul Bastard and colleagues have reported that in about 10% of patients with serious Covid-19, the interferon response gets crippled by the development of neutralising IgG auto-antibodies that attack IFNs itself at the onset of critical disease.

Interestingly, none of the 663 people in a control group with mild or asymptomatic Sars-CoV-2 infection had these rogue antibodies. An interesting feature of this study is that the majority of patients with IFN-attacking antibodies are males (94%) with half of the gravely ill being over 65 years of age. This helps explain why older men face a higher risk of severe disease.

The study raises an important possibility. Could synthetic IFNs given before or soon after the infection help block the virus before it causes severe disease? Interferon therapy has already been approved as immune-boosters in several diseases, including cancer and hepatitis. Several trials have already been initiated for Covid-19 at a dozen universities in the US and Europe and their results point to IFN safety and faster clearance of the virus, particularly if the therapy is initiated early.

The Covid-19-era has witnessed unprecedented swiftness in scientific collaboration. Several welcome possibilities have emerged and these have the potential to protect the high-risk health care workers, while also lessening the severity of Covid-19 in hospitalised patients until the vaccine becomes available.

Dr Narinder Kumar Mehra is Indian Council of Medical Research Emeritus Scientist (Hon) and former Dean, All India Institute of Medical Sciences, New Delhi

The views expressed are personal

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