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Emerging COVID-19 Variants Evade Antibody Treatments, Enhanced Therapies on the Horizon

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Monoclonal antibodies (mAbs) were touted as a key treatment against COVID-19 in 2020. However, as of 2023, with the evolution of SARS-CoV-2 and consequent drug resistance, the United States has withdrawn approvals for these antibodies. In response, scientists worldwide are reconfiguring antibody treatments to target less mutation-prone areas of the virus.

Researchers have been creating compounds that act as molecular Velcro, latching onto numerous sites on the viral proteins simultaneously. This strategy hinders the virus, even when some sites have mutated beyond the reach of drug candidates. There are also less radical strategies in the pipeline to create mutation-resistant antibodies.

Nevertheless, the urgency to bring these new treatments to the clinic might be declining. As the pandemic's emergency status is lifted in various countries, there's potential reluctance from governments and industries to fund new COVID-19 treatments.

The initial life-saving antibodies targeted the tip of the spike protein used by SARS-CoV-2 to attach to human cells. However, new variants with extensive mutations in the binding region have caused treatments to fail. The virus has been constantly evolving, making it challenging for antibodies to stay effective.

Presently, researchers aim to discover antibodies that target the parts of the spike protein which the virus cannot alter without affecting its infectivity. For example, several human antibodies targeting conserved spike protein regions have been isolated. These antibodies have shown effectiveness against multiple viral variants.

Alternative strategies are focusing on the human ACE2 protein that the virus attaches to. In a recent experiment, mice were injected with a potent antibody that targeted ACE2 and blocked SARS-CoV-2 from binding to it. This antibody was effective against multiple variants of the virus.

Yet another strategy aims to modify the structure of antibodies to enhance their potency. Novel 'multibodies' with 24 attachment sites have been designed. These multibodies have shown to neutralize the virus at lower doses than conventional antibodies.

While these results are promising, these strategies will need rigorous testing and further validation, as they are relatively new. Ensuring the new treatments are available and affordable will also be a challenge.

A decline in government aid and the huge investments required could potentially slow the commercialization of these new treatments. However, with a notable market in the form of immunocompromised individuals, who constitute about 3% of the US population, there's still a necessity for new treatments. Hence, it remains crucial to maintain momentum in the development of these novel therapies, despite the challenges.

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